What are Brain and Spinal Cord Tumors?Overview of the brain and spinal cordWhat causes CNS tumors?Who is at risk?How are tumors graded?What are the possible symptoms?How are CNS tumors diagnosed?How are brain and spinal cord tumors treated?

NeurosurgeryRadiation TherapyRadiosurgeryChemotherapyTargeted TherapyAlternative and Complementary Therapy

What Research is Being Done?Appendix: Some CNS Tumors and Tumor-Related ConditionsWhere can I get more information?

A tumor is a mass of abnormal cells that either form into a new growth or the growth was there when you were born (congenital). Tumors occur when something goes wrong with genes that regulate cell growth, allowing cells to grow and divide out of control. Tumors can form anywhere in your body. Brain and spinal cord tumors form in the tissue inside your brain or spinal cord, which make up the central nervous system (CNS).

Depending on its type, a growing tumor may not cause any symptoms or can killor displace healthy cells or disrupt their function. A tumor can move or press on sensitive tissue and block the flow of blood and other fluid, causing pain and inflammation. A tumor can also block the normal flow of activity in the brain or signaling to and from the brain. Some tumors dont cause any changes.Tumors can be noncancerous (benign) or cancerous (malignant).

Tumors can be primary or secondary.

There are more than 120 types of brain and spinal cord tumors. Some are named by the type of normal cell they most closely resemble or by location. Brain and spinal cord tumors are not contagious or, at this time, preventable.

See theAppendix at the end of this guide for a listing of some CNS tumors and tumor-related conditions.

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The brain has three major parts:

The brains two halves, or hemispheres, use nerve cells (neurons) to speak with each other.Each hemisphere has four sections, called lobes, which handle different neurological functions.

For more information, see General Information About Adult Central Nervous System Tumors.

The spinal cordan extension of the brainlies protected inside the bony spinal column. It contains bundles of nerves that carry messages between the brain and other parts of the body, such as instructions to move an arm or information from the skin that signals pain.

A tumor that forms on or near the spinal cord can disrupt communication between the brain and the nerves or restrict the cord's supply of blood. Because the spinal column is narrow, a tumor hereunlike a brain tumorcan cause symptoms on both sides of the body.

Spinal cord tumors, regardless of location, often cause pain, numbness, weakness or lack of coordination in the arms and legs, usually on both sides of the body. They also often cause bladder or bowel problems.

Spinal cord tumors are described based on where on the cord the tumor is located and each vertebra (part of a series of bones that form the backbone) is numbered from top to bottom. The neck region is called cervical (C), the back region is called thoracic (T), and the lower back region is called lumbar (L) or sacral/cauda equina (S). Tumors are further described by whether the tumor begins in the cells inside the spinal cord (intramedullary) or outside the spinal cord (extramedullary). Extramedullary tumors grow in the membrane surrounding the spinal cord (intradural) or outside (extradural).

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Researchers really don't know why primary brain and spinal cord tumors develop. Possible causes include viruses, defective genes, exposure to certain chemicals and other hazardous materials, and immune system disorders. Sometimes CNS tumors may result from specific genetic diseases, such as neurofibromatosis and tuberous sclerosis, or exposure to radiation.

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Anyone can develop a primary brain or spinal cord tumor, but the overall risk is very small. Brain tumors occur more often in males than in females and are most common in middle-aged to older persons. Although uncommon in children, brain tumors tend to occur more often in children under age 9, and some tumors tend to run in families. Most brain tumors in children are primary tumors.

Other risk factors for developing a primary brain or spinal cord tumor include race (Caucasians are more likely to develop a CNS tumor) and occupation. Workers in jobs that require repeated contact with ionizing radiation or certain chemicals, including those materials used in building supplies or plastics and textiles, have a greater chance of developing a brain tumor.

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The grade of a tumor may be used to tell the difference between slow-growing and fast-growing types of the tumor. The World Health Organization (WHO) tumor grades are based on how abnormal the cancer cells look under the microscope and how quickly the tumor is likely to grow and spread. Some tumors change grade as they progress, usually to a higher grade. The tumor is graded by a pathologist following a biopsy or during surgery.

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Brain and spinal cord tumors cause many different symptoms, which can make detection tricky. Symptoms depend on tumor type, location, size, and rate of growth. Certain symptoms are quite specific because they result from damage to particular areas of the brain and spinal cord. Symptoms generally develop slowly and worsen as the tumor grows.

Brain tumor

In infants, the most obvious sign of a brain tumor is a rapidly widening head or bulging crown. Other more common symptoms of a pediatric brain tumor can include:

In older children and adults, a tumor can cause a variety of symptoms, including headaches, seizures, balance problems, and personality changes.

Other symptoms may include endocrine disorders or abnormal hormonal regulation, difficulty swallowing, facial paralysis and sagging eyelids, fatigue, weakened sense of smell, or disrupted sleep and changes in sleep patterns.

Spinal cord tumors

Common symptoms of a spinal cord tumor include:

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If you are suspected of having a brain or spinal cord tumor, your doctor (usually a neurologist, oncologist, or neuro-oncologist) will perform a neurologic exam and may order a variety of tests based on your symptoms, personal and family medical history, and results of the physical exam. Once a tumor is found on diagnostic imaging studies, surgery to obtain tissue for a biopsy or removal is often recommended. Diagnosing the type of brain or spinal cord tumor is often difficult. Some tumor types are rare and the molecular and genetic alterations of some tumors are not well understood. You may want to ask your primary care doctor or oncologist for a second opinion from a comprehensive cancer center or neuro-oncologist with experience treating your diagnosis or tumor type. Even a secondopinion that confirms the originaldiagnosis can be reassuring and help you better prepare for your care and treatment.

A neurological exam

A neurological exam can be done in your doctors office. It assesses your movement and sensory skills, hearing and speech, reflexes, vision, coordination and balance, mental status, and changes in mood or behavior.

Some advanced tests are performed and analyzed by a specialist.

Diagnostic imaging

Diagnostic imaging produces extremely detailed views of structures inside the body, including tissues, organs, bones, and nerves. Such imagingcan confirm the diagnosis and helpdoctors determine the tumor's type, treatment options, and later, whether the treatment is working.

See the NINDS publication, Neurological Diagnostic Tests and Procedures, for a more complete description of the following tests:

Usually a contrast agent (such as a dye) is injected into a vein before a CT or MRI. Many tumors become much easier to identify on the scan after the contrast is given.

Laboratory and other tests

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A specialized team of doctors advises and assists individuals throughout treatment and rehabilitation. These doctors may include:

For more information, see: https://www.cancer.gov/rare-brain-spine-tumor/tumors/about-cns-tumors#who-treats-central-nervous-system-cns-tumors.

Your health care team will recommend a treatment plan based on the tumor's location, type, size and aggressiveness, as well as medical history, age, and general health. Malignant tumors require some form of treatment, while some small benign tumors may need onlymonitoring. Treatment for a brain or spinal tumor can include surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of treatments.Initial treatment for a CNS tumor may involve a variety of drugs to treat or ease symptoms, including:

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Surgery is usually the first treatment to both obtain tissue for diagnosis and remove as much tumor as can be done safely. Surgery may be the only treatment you need if your tumor is considered benign or low grade. Based on the type and grade (low versus high), doctors often recommend follow-up treatment, including radiation and chemotherapy, or an experimental treatment. You will be referred to the specialists above to provide guidance on this treatment.

Surgery is usually the first step in treating an accessible tumorone that can be removed without risk of neurological damage. Many low-grade tumors and secondary (metastatic) cancerous tumors can be removed entirely. Some tumors have a clearly defined shape and can be removed more easily. Your surgeon will try removing (called resecting or excising) all or as much tumor as possible. For malignant CNS tumors, this is best performed by a neurosurgeon.

An inaccessible or inoperable tumor is one that cannot be removed surgically because of the risk of severe nervous system damage during the operation. These tumors are frequently located deep within the brain or near vital structures such as the brain stem and may not have well-defined edges. In these cases, a biopsy may be performed.

A biopsy is sometimes performed to diagnose and help doctors determine how to treat a tumor. Biopsies can sometimes be performed by inserting a needle through a small hole in the body and taking a small piece of the tumor tissue. A pathologist will examine the tissue for certain changes that signal cancer and determine its stage or grade.

In some cases, a surgeon may need to insert a shunt into the skull to drain any dangerous buildup of CSF caused by the tumor. A shunt is a flexible plastic tube that is used to divert the flow of CSF from the central nervous system to another part of the body, where it can be absorbed as part of the normal circulatory process.

During surgery, some tools used in the operating room include a surgical microscope, the endoscope (a small viewing tube attached to a video camera), and miniature precision instruments that allow surgery to be performed through a small incision in the brain or spine. Other tools include:

For more information, see: Surgery to Treat Cancer.

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Radiation therapy usually involvesrepeated doses of high-energy beams such as x-rays or protons to kill cancer cells or keep them from multiplying. Radiation therapy can shrink the tumor mass. It can be used to treat surgically inaccessible tumors or tumor cells that may remain following surgery.

Radiation treatment can be delivered externally, using focused beams of energy or charged particles that are directed at the tumor, or from inside the body, using a surgically implanted device. The stronger the radiation, the deeper it can penetrate to the target site. Healthy cells may also be damaged by radiation therapy, but current radiation treatment is designed to minimize injury to normal tissue.

Treatment often begins soon after surgery and may continue for several weeks. Depending on the tumor type and location, a person may be able to receive a modified form of therapy to lessen damage to healthy cells and improve the overall treatment.

Externally delivered radiation therapy poses no risk of radioactivity to the person or family and friends. Types of external radiation therapy include:

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Radiosurgery is usually a one-time treatment using multiple, sharply focused radiation beams aimed at the brain or spinal cord tumor from multiple angles.It does not cut into the person but, like other forms of radiation therapy, harms a tumor cells ability to grow and divide. It is commonly used to treat surgically inaccessible tumors and maybe used at the end of conventional radiation treatment. Two common radiosurgery procedures are:

Side effects of radiation: Side effects of radiation therapy vary from person to person and are usually temporary. They typically begin about two weeks after treatment starts and may include fatigue, nausea, vomiting, reddened or sore skin in the treated area, headache, hearing loss, problems with sleep, and hair loss (although the hair usually grows back once the treatment has stopped). Radiation therapy in young children, particularly those age three years or younger, can cause problems with learning, processing information, thinking, and growing.

There are late side effects of radiation that may occur months to years after treatment that include shrinkage (atrophy) of the brain or spinal cord region that was treated.

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Chemotherapy uses powerful drugs to kill cancer cells or stop them from growing or spreading. These drugs are usually given orally, intravenously, or through a catheter or port and travel through the body to the cancerous cells. Your oncologist will recommend a treatment plan based on the type of cancer, drug(s) to be used, the frequency of administration, and the number of cycles needed. Chemotherapy is given in cycles to more effectively damage and kill cancer cells and give normal cells time to recover from any damage.

Individuals might receive chemotherapy to shrink the tumor before surgery called neo-adjuvant therapy (a first step treatment to shrink a tumor before the primary treatment). Radiation therapy can also be given as neo-adjuvant therapy. After surgery, or radiation treatment if radiation is the primary treatment, chemotherapy could be called adjuvant therapy (treatment in addition to the primary treatment). Metronomic therapy involves continuous low-dose chemotherapy to block mechanisms that stimulate the growth of new blood vessels needed to feed the tumor.

Not all tumors are vulnerable to the same anticancer drugs, so a persons treatment may include a combination of drugs. Common CNS chemotherapies include temozolomide, carmustine (also called BCNU), lomustine (also called CCNU), and bevacizumab. Individuals should be sure to discuss all options with their medical team.

Side effects of chemotherapy may include hair loss, nausea, digestive problems, reduced bone marrow production, and fatigue. The treatment can also harm normal cells that are growing or dividing at the same time, but these cells usually recover and side effects often improve or stop once the treatment has ended.

For more information about chemotherapy, see: Chemotherapy to Treat Cancer .

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Targeted therapy is a cancer treatment that uses drugs to target specific genes and proteins that are involved in tumor cell growth. This helps slow uncontrolled growth and reduce the production of tumor cells. Targeted therapies include oncogenes, growth factors, and molecules aimed at blocking gene activity.

Alternative and complementary approaches may help tumor patients better cope with their diagnosis and treatment. Some of these therapies, however, may be harmful if used during or after cancer treatment and should be discussed in advance with a doctor. Common approaches include nutritional and herbal supplements, vitamins, special diets, and mental or physical techniques to reduce stress.

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Scientists continue to investigate ways to better understand, diagnose, and treat CNS tumors. Several of todays treatments were experimental therapies only a decade ago.Clinical studies are research studies that test or observe how well medical approaches work in people.Some clinical studies test new treatments such as a new drug or medical therapy. Treatment studies help researchers learn if a new treatment is effective or less harmful than standard treatments. Studies can be considered at any point, from the time of diagnosis through recurrence. For more information about clinical studies, see: National Cancer Institute Clinical Trials.

Current clinical studies of genetic risk factors, environmental causes, and molecular mechanisms of cancers may translate into tomorrows treatment of, or perhaps cure for, these tumors.Much of this work is supported by the National Institutes of Health (NIH), through the collaborative efforts of its National Institute of Neurological Disorders and Stroke (NINDS) and National Cancer Institute (NCI), as well as other federal agencies, nonprofit groups, pharmaceutical companies, and private institutions. Some of this research is conducted through the collaborative neuroscience and cancer research community at the NIH or through research grants to academic centers throughout the United States.

The jointly sponsored NCI-NINDS Neuro-Oncology Branch coordinates research to develop and test the effectiveness and safety of novel therapies for people with CNS tumors. These experimental treatment options may include new drugs, combination therapy, gene therapy, advanced imaging and artificial intelligence, biologic immuno-agents, surgery, and radiation. Information about these trials, and trials for other disorders, can be accessed at the federal governments database of clinical trials, ClinicalTrials.gov.

Scientists at NIH and universities across the United States are exploring a variety of approaches to treat CNS tumors. These experimental approaches include boosting the immune system to better fight tumor cells, developing therapies that target the tumor cell while sparing normal cells,making improvementsin radiation therapy, disabling the tumor using genes attached to viruses, and defining biomarkers that may predict the response of a CNS tumor to a particular treatment.

Biological therapy (also called immunotherapy)involves enhancing the bodys overall immune response to recognize and fight cancer cells. The immune system is designed to attack foreign substances in the body, but because cancer cells arent foreign, they usually do not generate much of an immune response. Researchers are using different methods to provoke a strong immune response to tumor cells, including:

Targeted therapy uses molecularly targeted drugs that seek out the cellular changes that convert normal cells into cancer. Targeted therapies include:

Biomarkersare molecules or other substances in the blood or tissue that can be used to diagnose or monitor a disorder. Some CNS tumor biomarkers have been found, such as the epithelial growth factor receptor (EGRF) gene. Researchers continue to search for additional clinical biomarkers of CNS tumors, to better assess risk from environmental toxins and other possible causes and monitor and predict the outcome of CNS tumor treatment. Identifying biomarkers may also lead to the development of new disease models and novel therapies for tumor treatment.

Radiation therapyresearch includes testing several new anticancer drugs, either independently or in combination with other drugs. Researchers are also investigating combined therapies including drugs, radiation, and radiosurgery to effectively treat CNS tumors. Research areas under investigation include radiosensitizersdrugs that make rapidly dividing tumor tissue more vulnerable to radiation.

Chemotherapeutic drugresearch focuses on ways to better deliver drugsacross the blood-brain barrier and into the site of the tumor. Since chemotherapeutic drugs work in different ways to stop tumor cells from dividing, several trials are testing whether giving more than one drug, and perhaps giving them in different ways (such as staggered delivery and low-dose, long-term treatment), may kill more tumor cells without causing damaging side effects than present therapy. Researchers are examining different levels of chemotherapeutic drugs to determine whether they are less toxic to normal tissue when combined with other cancer treatments, and ways to make cancer cells more sensitive to chemotherapy. Research areas include:

Surgery studies are ongoing to better define the potential benefits of surgery, including better response to biologic therapy and chemotherapy, improved quality of life, and prolonged survival.

Clinical trials can help doctors and scientists discover whether new treatments are effective and safe for many people with spinal and brain tumors. Both healthy people and those with a disease participate in clinical trials, which increases our understanding about diseases including brain and spinal tumors. To learn more about clinical trials for CNS tumors and how to participate in them, visit http://www.clinicaltrials.gov, a database of thousands of studies, some of which include results and papers on findings.

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There are many types of brain and spinal cord tumors. These tumors are named by their location in the body, cell of origin, rate of growth, and malignancy. Some tumor types are more prevalent in children than in adults. Here is a listing of some common benign and malignant CNS tumors.

Glioma

Glioma tumorsgrow from several types of glial cells, which support the function of neurons. Gliomasusually occur in the brains cerebral hemispheres but may also strike other areas. Gliomas are classified based on the type of normal glial cells they resemble.

Mixed gliomas contain more than one type of glial cell and are usually found in the cerebrum. These tumors can spread to other sites in the brain.Other gliomas are named after the part of the body they affect. Among them are:

ChordomaChordomas are rare congenital tumors which develop from remnants of the flexible spine-like structure that forms and dissolves early in fetal development (and is later replaced by the bones of the spine). Chordomas often occur near the top or the bottom of the spine, outside the dura mater, and can invade the spinal canal and skull cavity.

Choroid plexus papillomaThis rare, usually benign childhood tumor develops slowly and can increase the production and block the flow of CSF, causing symptoms that include headaches and increased intracranial pressure. A rarer cancerous form can spread via the cerebrospinal fluid.

Germ cell tumorsThese very rare childhood tumors may start in cells that fail to leave the CNS during development. Germ cell tumors usually form in the center of the brain and can spread elsewhere in the brain and spinal cord. Different tumors are named after the type of germ cell.

MeningiomaMeningiomas are benign tumors that develop from the thin membranes, or meninges, that cover the brain and spinal cord. Meningiomas usually grow slowly, generally do not invade surrounding normal tissue, and rarely spread to other parts of the CNS or body.

Pineal TumorsThese tumors form in the pineal gland, a small structure located between the cerebellum and the cerebrum. The three most common types of pineal region tumors are gliomas, germ cell tumors, and pineal cell tumors

Pituitary Tumors (also called pituitary adenomas)These small tumors form in the pituitary gland. Most pituitary tumors are benign and their incidence increases with age. Pituitary tumors are classified as either non-secreting or secreting (secreting tumors release unusually high levels of pituitary hormones, which can trigger neurological conditions and symptoms including Cushings syndromea harmful overproduction of the hormone cortisol).

Primitive Neuroectodermal Tumors (PNET)These malignant tumors may spring from primitive or immature cells left over from early development of the nervous system. PNETS can spread throughout the brain and spinal cord in a scattered, patchy pattern and, in rare cases, cause cancer outside the CNS. The two most common PNETs are:

Vascular TumorsThese rare, noncancerous tumors arise from the blood vessels of the brain and spinal cord. The most common vascular tumor is the hemangioblastoma, a cyst-like mass of tangled blood vessels, which does not usually spread.

For information on some rare brain and spinal cord tumors, see: https://www.cancer.gov/rare-brain-spine-tumor/tumors.

Arachnoid cystsare benign, fluid-filled masses that form within a thin membrane lining (tumors are solid tissue masses). Cysts in the CNS can cause tumor-like symptoms including headache and seizures. Some cysts occur more often in the spinal cord than in the brain, and certain cysts are seen most frequently in children.

Hydrocephalusinvolves the build-up of cerebrospinal fluid in the brain. The excessive fluidcan cause harmful pressure, headaches, and nausea.

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January 3rd, 2023

14.3 The Brain and Spinal Cord Anatomy & Physiology

By daniellenierenberg

Learning Objectives

By the end of this section, you will be able to:

The brain and the spinal cord are the central nervous system, and they represent the main organs of the nervous system. The spinal cord is a single structure, whereas the adult brain is described in terms of four major regions: the cerebrum, the diencephalon, the brain stem, and the cerebellum. A persons conscious experiences are based on neural activity in the brain. The regulation of homeostasis is governed by a specialized region in the brain. The coordination of reflexes depends on the integration of sensory and motor pathways in the spinal cord.

The iconic gray mantle of the human brain, which appears to make up most of the mass of the brain, is the cerebrum (Figure 14.3.1). The wrinkled portion is the cerebral cortex, and the rest of the structure is beneath that outer covering. There is a large separation between the two sides of the cerebrum called the longitudinal fissure. It separates the cerebrum into two distinct halves, a right and left cerebral hemisphere. Deep within the cerebrum, the white matter of the corpus callosum provides the major pathway for communication between the two hemispheres of the cerebral cortex.

Many of the higher neurological functions, such as memory, emotion, and consciousness, are the result of cerebral function. The complexity of the cerebrum is different across vertebrate species. The cerebrum of the most primitive vertebrates is not much more than the connection for the sense of smell. In mammals, the cerebrum comprises the outer gray matter that is the cortex (from the Latin word meaning bark of a tree) and several deep nuclei that belong to three important functional groups. The basal nuclei are responsible for cognitive processing, the most important function being that associated with planning movements. The basal forebrain contains nuclei that are important in learning and memory. The limbic cortex is the region of the cerebral cortex that is part of the limbic system, a collection of structures involved in emotion, memory, and behavior.

The cerebrum is covered by a continuous layer of gray matter that wraps around either side of the forebrainthe cerebral cortex. This thin, extensive region of wrinkled gray matter is responsible for the higher functions of the nervous system. A gyrus (plural = gyri) is the ridge of one of those wrinkles, and a sulcus (plural = sulci) is the groove between two gyri. The pattern of these folds of tissue indicates specific regions of the cerebral cortex.

The head is limited by the size of the birth canal, and the brain must fit inside the cranial cavity of the skull. Extensive folding in the cerebral cortex enables more gray matter to fit into this limited space. If the gray matter of the cortex were peeled off of the cerebrum and laid out flat, its surface area would be roughly equal to one square meter.

The folding of the cortex maximizes the amount of gray matter in the cranial cavity. During embryonic development, as the telencephalon expands within the skull, the brain goes through a regular course of growth that results in everyones brain having a similar pattern of folds. The surface of the brain can be mapped on the basis of the locations of large gyri and sulci. Using these landmarks, the cortex can be separated into four major regions, or lobes (Figure 14.3.2). The lateral sulcus that separates the temporal lobe from the other regions is one such landmark. Superior to the lateral sulcus are the parietal lobe and frontal lobe, which are separated from each other by the central sulcus. The posterior region of the cortex is the occipital lobe, which has no obvious anatomical border between it and the parietal or temporal lobes on the lateral surface of the brain. From the medial surface, an obvious landmark separating the parietal and occipital lobes is called the parieto-occipital sulcus. The fact that there is no obvious anatomical border between these lobes is consistent with the functions of these regions being interrelated.

Different regions of the cerebral cortex can be associated with particular functions, a concept known as localization of function. In the early 1900s, a German neuroscientist named Korbinian Brodmann performed an extensive study of the microscopic anatomythe cytoarchitectureof the cerebral cortex and divided the cortex into 52 separate regions on the basis of the histology of the cortex. His work resulted in a system of classification known as Brodmanns areas, which is still used today to describe the anatomical distinctions within the cortex (Figure 14.3.3). The results from Brodmanns work on the anatomy align very well with the functional differences within the cortex. Areas 17 and 18 in the occipital lobe are responsible for primary visual perception. That visual information is complex, so it is processed in the temporal and parietal lobes as well.

The temporal lobe is associated with primary auditory sensation, known as Brodmanns areas 41 and 42 in the superior temporal lobe. Because regions of the temporal lobe are part of the limbic system, memory is an important function associated with that lobe. Memory is essentially a sensory function; memories are recalled sensations such as the smell of Moms baking or the sound of a barking dog. Even memories of movement are really the memory of sensory feedback from those movements, such as stretching muscles or the movement of the skin around a joint. Structures in the temporal lobe are responsible for establishing long-term memory, but the ultimate location of those memories is usually in the region in which the sensory perception was processed.

The main sensation associated with the parietal lobe is somatosensation, meaning the general sensations associated with the body. Posterior to the central sulcus is the postcentral gyrus, the primary somatosensory cortex, which is identified as Brodmanns areas 1, 2, and 3. All of the tactile senses are processed in this area, including touch, pressure, tickle, pain, itch, and vibration, as well as more general senses of the body such as proprioception and kinesthesia, which are the senses of body position and movement, respectively.

Anterior to the central sulcus is the frontal lobe, which is primarily associated with motor functions. The precentral gyrus is the primary motor cortex. Cells from this region of the cerebral cortex are the upper motor neurons that instruct cells in the spinal cord and brain stem (lower motor neurons) to move skeletal muscles. Anterior to this region are a few areas that are associated with planned movements. The premotor area is responsible for storing learned movement algorithms which are instructions for complex movements. Different algorithmsactivate the upper motor neurons in the correct sequence when a complex motor activity is performed.The frontal eye fields are important in eliciting scanning eye movements and in attending to visual stimuli. Brocas area is responsible for the production of language, or controlling movements responsible for speech; in the vast majority of people, it is located only on the left side. Anterior to these regions is the prefrontal lobe, which serves cognitive functions that can be the basis of personality, short-term memory, and consciousness. The prefrontal lobotomy is an outdated mode of treatment for personality disorders (psychiatric conditions) that profoundly affected the personality of the patient.

Area 17, as Brodmann described it, is also known as the primary visual cortex. Adjacent to that are areas 18 and 19, which constitute subsequent regions of visual processing. Area 22 is the primary auditory cortex, and it is followed by area 23, which further processes auditory information. Area 4 is the primary motor cortex in the precentral gyrus, whereas area 6 is the premotor cortex. These areas suggest some specialization within the cortex for functional processing, both in sensory and motor regions. The fact that Brodmanns areas correlate so closely to functional localization in the cerebral cortex demonstrates the strong link between structure and function in these regions.

Areas 1, 2, 3, 4, 17, and 22 are each described as primary cortical areas. The adjoining regions are each referred to as association areas. Primary areas are where sensory information is initially received from the thalamus for conscious perception, orin the case of the primary motor cortexwhere descending commands are sent down to the brain stem or spinal cord to execute movements (Figure 14.3.4).

The cerebrum is the seat of many of the higher mental functions, such as memory and learning, language, and conscious perception, which are the subjects of subtests of the mental status exam. The cerebral cortex is the thin layer of gray matter on the outside of the cerebrum. It is approximately a millimeter thick in most regions and highly folded to fit within the limited space of the cranial vault. These higher functions are distributed across various regions of the cortex, and specific locations can be said to be responsible for particular functions. There is a limited set of regions, for example, that are involved in language function, and they can be subdivided on the basis of the particular part of language function that each governs.

A number of other regions, which extend beyond these primary or association areas of the cortex, are referred to as integrative areas. These areas are found in the spaces between the domains for particular sensory or motor functions, and they integrate multisensory information, or process sensory or motor information in more complex ways. Consider, for example, the posterior parietal cortex that lies between the somatosensory cortex and visual cortex regions. This has been ascribed to the coordination of visual and motor functions, such as reaching to pick up a glass. The somatosensory function that would be part of this is the proprioceptive feedback from moving the arm and hand. The weight of the glass, based on what it contains, will influence how those movements are executed.

Assessment of cerebral functions is directed at cognitive abilities. The abilities assessed through the mental status exam can be separated into four groups: orientation and memory, language and speech, sensorium, and judgment and abstract reasoning.

Orientation is the patients awareness of his or her immediate circumstances. It is awareness of time, not in terms of the clock, but of the date and what is occurring around the patient. It is awareness of place, such that a patient should know where he or she is and why. It is also awareness of who the patient isrecognizing personal identity and being able to relate that to the examiner. The initial tests of orientation are based on the questions, Do you know what the date is? or Do you know where you are? or What is your name? Further understanding of a patients awareness of orientation can come from questions that address remote memory, such as Who is the President of the United States?, or asking what happened on a specific date.

There are also specific tasks to address memory. One is the three-word recall test. The patient is given three words to recall, such as book, clock, and shovel. After a short interval, during which other parts of the interview continue, the patient is asked to recall the three words. Other tasks that assess memoryaside from those related to orientationhave the patient recite the months of the year in reverse order to avoid the overlearned sequence and focus on the memory of the months in an order, or to spell common words backwards, or to recite a list of numbers back.

Memory is largely a function of the temporal lobe, along with structures beneath the cerebral cortex such as the hippocampus and the amygdala. The storage of memory requires these structures of the medial temporal lobe. A famous case of a man who had both medial temporal lobes removed to treat intractable epilepsy provided insight into the relationship between the structures of the brain and the function of memory.

Henry Molaison, who was referred to as patient HM when he was alive, had epilepsy localized to both of his medial temporal lobes. In 1953, a bilateral lobectomy was performed that alleviated the epilepsy but resulted in the inability for HM to form new memoriesa condition called anterograde amnesia. HM was able to recall most events from before his surgery, although there was a partial loss of earlier memories, which is referred to as retrograde amnesia. HM became the subject of extensive studies into how memory works. What he was unable to do was form new memories of what happened to him, what are now called episodic memory. Episodic memory is autobiographical in nature, such as remembering riding a bicycle as a child around the neighborhood, as opposed to the procedural memory of how to ride a bike. HM also retained his short-term memory, such as what is tested by the three-word task described above. After a brief period, those memories would dissipate or decay and not be stored in the long-term because the medial temporal lobe structures were removed.

The difference in short-term, procedural, and episodic memory, as evidenced by patient HM, suggests that there are different parts of the brain responsible for those functions. The long-term storage of episodic memory requires the hippocampus and related medial temporal structures, and the location of those memories is in the multimodal integration areas of the cerebral cortex. However, short-term memoryalso called working or active memoryis localized to the prefrontal lobe. Because patient HM had only lost his medial temporal lobeand lost very little of his previous memories, and did not lose the ability to form new short-term memoriesit was concluded that the function of the hippocampus, and adjacent structures in the medial temporal lobe, is to move (or consolidate) short-term memories (in the pre-frontal lobe) to long-term memory (in the temporal lobe).

The prefrontal cortex can also be tested for the ability to organize information. In one subtest of the mental status exam called set generation, the patient is asked to generate a list of words that all start with the same letter, but not to include proper nouns or names. The expectation is that a person can generate such a list of at least 10 words within 1 minute. Many people can likely do this much more quickly, but the standard separates the accepted normal from those with compromised prefrontal cortices.

Read this article to learn about a young man who texts his fiance in a panic as he finds that he is having trouble remembering things. At the hospital, a neurologist administers the mental status exam, which is mostly normal except for the three-word recall test. The young man could not recall them even 30 seconds after hearing them and repeating them back to the doctor. An undiscovered mass in the mediastinum region was found to be Hodgkins lymphoma, a type of cancer that affects the immune system and likely caused antibodies to attack the nervous system. The patient eventually regained his ability to remember, though the events in the hospital were always elusive. Considering that the effects on memory were temporary, but resulted in the loss of the specific events of the hospital stay, what regions of the brain were likely to have been affected by the antibodies and what type of memory does that represent?

Language is, arguably, a very human aspect of neurological function. There are certainly strides being made in understanding communication in other species, but much of what makes the human experience seemingly unique is its basis in language. Any understanding of our species is necessarily reflective, as suggested by the question What am I? And the fundamental answer to this question is suggested by the famous quote by Ren Descartes: Cogito Ergo Sum (translated from Latin as I think, therefore I am). Formulating an understanding of yourself is largely describing who you are to yourself. It is a confusing topic to delve into, but language is certainly at the core of what it means to be self-aware.

The neurological exam has two specific subtests that address language. One measures the ability of the patient to understand language by asking them to follow a set of instructions to perform an action, such as touch your right finger to your left elbow and then to your right knee. Another subtest assesses the fluency and coherency of language by having the patient generate descriptions of objects or scenes depicted in drawings, and by reciting sentences or explaining a written passage. Language, however, is important in so many ways in the neurological exam. The patient needs to know what to do, whether it is as simple as explaining how the knee-jerk reflex is going to be performed, or asking a question such as What is your name? Often, language deficits can be determined without specific subtests; if a person cannot reply to a question properly, there may be a problem with the reception of language.

An important example of multimodal integrative areas is associated with language function (Figure 14.3.5). Adjacent to the auditory association cortex, at the end of the lateral sulcus just anterior to the visual cortex, is Wernickes area. In the lateral aspect of the frontal lobe, just anterior to the region of the motor cortex associated with the head and neck, is Brocas area. Both regions were originally described on the basis of losses of speech and language, which is called aphasia. The aphasia associated with Brocas area is known as an expressive aphasia, which means that speech production is compromised. This type of aphasia is often described as non-fluency because the ability to say some words leads to broken or halting speech. Grammar can also appear to be lost. The aphasia associated with Wernickes area is known as a receptive aphasia, which is not a loss of speech production, but a loss of understanding of content. Patients, after recovering from acute forms of this aphasia, report not being able to understand what is said to them or what they are saying themselves, but they often cannot keep from talking.

The two regions are connected by white matter tracts that run between the posterior temporal lobe and the lateral aspect of the frontal lobe. Conduction aphasia associated with damage to this connection refers to the problem of connecting the understanding of language to the production of speech. This is a very rare condition, but is likely to present as an inability to faithfully repeat spoken language.

Those parts of the brain involved in the reception and interpretation of sensory stimuli are referred to collectively as the sensorium. The cerebral cortex has several regions that are necessary for sensory perception. From the primary cortical areas of the somatosensory, visual, auditory, and gustatory senses to the association areas that process information in these modalities, the cerebral cortex is the seat of conscious sensory perception. In contrast, sensory information can also be processed by deeper brain regions, which we may vaguely describe as subconsciousfor instance, we are not constantly aware of the proprioceptive information that the cerebellum uses to maintain balance. Several of the subtests can reveal activity associated with these sensory modalities, such as being able to hear a question or see a picture. Two subtests assess specific functions of these cortical areas.

The first is praxis, a practical exercise in which the patient performs a task completely on the basis of verbal description without any demonstration from the examiner. For example, the patient can be told to take their left hand and place it palm down on their left thigh, then flip it over so the palm is facing up, and then repeat this four times. The examiner describes the activity without any movements on their part to suggest how the movements are to be performed. The patient needs to understand the instructions, transform them into movements, and use sensory feedback, both visual and proprioceptive, to perform the movements correctly.

The second subtest for sensory perception is gnosis, which involves two tasks. The first task, known as stereognosis, involves the naming of objects strictly on the basis of the somatosensory information that comes from manipulating them. The patient keeps their eyes closed and is given a common object, such as a coin, that they have to identify. The patient should be able to indicate the particular type of coin, such as a dime versus a penny, or a nickel versus a quarter, on the basis of the sensory cues involved. For example, the size, thickness, or weight of the coin may be an indication, or to differentiate the pairs of coins suggested here, the smooth or corrugated edge of the coin will correspond to the particular denomination. The second task, graphesthesia, is to recognize numbers or letters written on the palm of the hand with a dull pointer, such as a pen cap.

Praxis and gnosis are related to the conscious perception and cortical processing of sensory information. Being able to transform verbal commands into a sequence of motor responses, or to manipulate and recognize a common object and associate it with a name for that object. Both subtests have language components because language function is integral to these functions. The relationship between the words that describe actions, or the nouns that represent objects, and the cerebral location of these concepts is suggested to be localized to particular cortical areas. Certain aphasias can be characterized by a deficit of verbs or nouns, known as V impairment or N impairment, or may be classified as VN dissociation. Patients have difficulty using one type of word over the other. To describe what is happening in a photograph as part of the expressive language subtest, a patient will use active- or image-based language. The lack of one or the other of these components of language can relate to the ability to use verbs or nouns. Damage to the region at which the frontal and temporal lobes meet, including the region known as the insula, is associated with V impairment; damage to the middle and inferior temporal lobe is associated with N impairment.

Planning and producing responses requires an ability to make sense of the world around us. Making judgments and reasoning in the abstract are necessary to produce movements as part of larger responses. For example, when your alarm goes off, do you hit the snooze button or jump out of bed? Is 10 extra minutes in bed worth the extra rush to get ready for your day? Will hitting the snooze button multiple times lead to feeling more rested or result in a panic as you run late? How you mentally process these questions can affect your whole day.

The prefrontal cortex is responsible for the functions responsible for planning and making decisions. In the mental status exam, the subtest that assesses judgment and reasoning is directed at three aspects of frontal lobe function. First, the examiner asks questions about problem solving, such as If you see a house on fire, what would you do? The patient is also asked to interpret common proverbs, such as Dont look a gift horse in the mouth. Additionally, pairs of words are compared for similarities, such as apple and orange, or lamp and cabinet.

The prefrontal cortex is composed of the regions of the frontal lobe that are not directly related to specific motor functions. The most posterior region of the frontal lobe, the precentral gyrus, is the primary motor cortex. Anterior to that are the premotor cortex, Brocas area, and the frontal eye fields, which are all related to planning certain types of movements. Anterior to what could be described as motor association areas are the regions of the prefrontal cortex. They are the regions in which judgment, abstract reasoning, and working memory are localized. The antecedents to planning certain movements are judging whether those movements should be made, as in the example of deciding whether to hit the snooze button.

To an extent, the prefrontal cortex may be related to personality. The neurological exam does not necessarily assess personality, but it can be within the realm of neurology or psychiatry. A clinical situation that suggests this link between the prefrontal cortex and personality comes from the story of Phineas Gage, the railroad worker from the mid-1800s who had a metal spike impale his prefrontal cortex. There are suggestions that the steel rod led to changes in his personality. A man who was a quiet, dependable railroad worker became a raucous, irritable drunkard. Later anecdotal evidence from his life suggests that he was able to support himself, although he had to relocate and take on a different career as a stagecoach driver.

A psychiatric practice to deal with various disorders was the prefrontal lobotomy. This procedure was common in the 1940s and early 1950s, until antipsychotic drugs became available. The connections between the prefrontal cortex and other regions of the brain were severed. The disorders associated with this procedure included some aspects of what are now referred to as personality disorders, but also included mood disorders and psychoses. Depictions of lobotomies in popular media suggest a link between cutting the white matter of the prefrontal cortex and changes in a patients mood and personality, though this correlation is not well understood.

Popular media often refer to right-brained and left-brained people, as if the brain were two independent halves that work differently for different people. This is a popular misinterpretation of an important neurological phenomenon. As an extreme measure to deal with a debilitating condition, the corpus callosum may be sectioned to overcome intractable epilepsy. When the connections between the two cerebral hemispheres are cut, interesting effects can be observed.

If a person with an intact corpus callosum is asked to put their hands in their pockets and describe what is there on the basis of what their hands feel, they might say that they have keys in their right pocket and loose change in the left. They may even be able to count the coins in their pocket and say if they can afford to buy a candy bar from the vending machine. If a person with a sectioned corpus callosum is given the same instructions, they will do something quite peculiar. They will only put their right hand in their pocket and say they have keys there. They will not even move their left hand, much less report that there is loose change in the left pocket.

The reason for this is that the language functions of the cerebral cortex are localized to the left hemisphere in 95 percent of the population. Additionally, the left hemisphere is connected to the right side of the body through the corticospinal tract and the ascending tracts of the spinal cord. Motor commands from the precentral gyrus control the opposite side of the body, whereas sensory information processed by the postcentral gyrus is received from the opposite side of the body. For a verbal command to initiate movement of the right arm and hand, the left side of the brain needs to be connected by the corpus callosum. Language is processed in the left side of the brain and directly influences the left brain and right arm motor functions, but is sent to influence the right brain and left arm motor functions through the corpus callosum. Likewise, the left-handed sensory perception of what is in the left pocket travels across the corpus callosum from the right brain, so no verbal report on those contents would be possible if the hand happened to be in the pocket.

Watch the video titled The Man With Two Brains to see the neuroscientist Michael Gazzaniga introduce a patient he has worked with for years who has had his corpus callosum cut, separating his two cerebral hemispheres. A few tests are run to demonstrate how this manifests in tests of cerebral function. Unlike normal people, this patient can perform two independent tasks at the same time because the lines of communication between the right and left sides of his brain have been removed. Whereas a person with an intact corpus callosum cannot overcome the dominance of one hemisphere over the other, this patient can. If the left cerebral hemisphere is dominant in the majority of people, why would right-handedness be most common?

The cerebrum, particularly the cerebral cortex, is the location of important cognitive functions that are the focus of the mental status exam. The regionalization of the cortex, initially described on the basis of anatomical evidence of cytoarchitecture, reveals the distribution of functionally distinct areas. Cortical regions can be described as primary sensory or motor areas, association areas, or multimodal integration areas. The functions attributed to these regions include attention, memory, language, speech, sensation, judgment, and abstract reasoning.

The mental status exam addresses these cognitive abilities through a series of subtests designed to elicit particular behaviors ascribed to these functions. The loss of neurological function can illustrate the location of damage to the cerebrum. Memory functions are attributed to the temporal lobe, particularly the medial temporal lobe structures known as the hippocampus and amygdala, along with the adjacent cortex. Evidence of the importance of these structures comes from the side effects of a bilateral temporal lobectomy that were studied in detail in patient HM.

Losses of language and speech functions, known as aphasias, are associated with damage to the important integration areas in the left hemisphere known as Brocas or Wernickes areas, as well as the connections in the white matter between them. Different types of aphasia are named for the particular structures that are damaged. Assessment of the functions of the sensorium includes praxis and gnosis. The subtests related to these functions depend on multimodal integration, as well as language-dependent processing.

The prefrontal cortex contains structures important for planning, judgment, reasoning, and working memory. Damage to these areas can result in changes to personality, mood, and behavior. The famous case of Phineas Gage suggests a role for this cortex in personality, as does the outdated practice of prefrontal lobectomy.

Beneath the cerebral cortex are sets of nuclei known as subcortical nuclei that augment cortical processes. The nuclei of the basal forebrain serve as the primary location for acetylcholine production, which modulates the overall activity of the cortex, possibly leading to greater attention to sensory stimuli. Alzheimers disease is associated with a loss of neurons in the basal forebrain. The hippocampus and amygdala are medial-lobe structures that, along with the adjacent cortex, are involved in long-term memory formation and emotional responses. The basal nuclei are a set of nuclei in the cerebrum responsible for comparing cortical processing with the general state of activity in the nervous system to influence the likelihood of movement taking place. For example, while a student is sitting in a classroom listening to a lecture, the basal nuclei will keep the urge to jump up and scream from actually happening. (The basal nuclei are also referred to as the basal ganglia, although that is potentially confusing because the term ganglia is typically used for peripheral structures.)

The major structures of the basal nuclei that control movement are the caudate, putamen, and globus pallidus, which are located deep in the cerebrum. The caudate is a long nucleus that follows the basic C-shape of the cerebrum from the frontal lobe, through the parietal and occipital lobes, into the temporal lobe. The putamen is mostly deep in the anterior regions of the frontal and parietal lobes. Together, the caudate and putamen are called the striatum. The globus pallidus is a layered nucleus that lies just medial to the putamen; they are called the lenticular nuclei because they look like curved pieces fitting together like lenses. The globus pallidus has two subdivisions, the external and internal segments, which are lateral and medial, respectively. These nuclei are depicted in a frontal section of the brain in Figure 14.3.6.

The basal nuclei in the cerebrum are connected with a few more nuclei in the brain stem that together act as a functional group that forms a motor pathway. Two streams of information processing take place in the basal nuclei. All input to the basal nuclei is from the cortex into the striatum (Figure 14.3.7). The direct pathway is the projection of axons from the striatum to the globus pallidus internal segment (GPi) and the substantia nigra pars reticulata (SNr). The GPi/SNr then projects to the thalamus, which projects back to the cortex. The indirect pathway is the projection of axons from the striatum to the globus pallidus external segment (GPe), then to the subthalamic nucleus (STN), and finally to GPi/SNr. The two streams both target the GPi/SNr, but one has a direct projection and the other goes through a few intervening nuclei. The direct pathway causes the disinhibition of the thalamus (inhibition of one cell on a target cell that then inhibits the first cell), whereas the indirect pathway causes, or reinforces, the normal inhibition of the thalamus. The thalamus then can either excite the cortex (as a result of the direct pathway) or fail to excite the cortex (as a result of the indirect pathway).

The switch between the two pathways is the substantia nigra pars compacta, which projects to the striatum and releases the neurotransmitter dopamine. Dopamine receptors are either excitatory (D1-type receptors) or inhibitory (D2-type receptors). The direct pathway is activated by dopamine, and the indirect pathway is inhibited by dopamine. When the substantia nigra pars compacta is firing, it signals to the basal nuclei that the body is in an active state, and movement will be more likely. When the substantia nigra pars compacta is silent, the body is in a passive state, and movement is inhibited. To illustrate this situation, while a student is sitting listening to a lecture, the substantia nigra pars compacta would be silent and the student less likely to get up and walk around. Likewise, while the professor is lecturing, and walking around at the front of the classroom, the professors substantia nigra pars compacta would be active, in keeping with his or her activity level.

Watch this video to learn about the basal nuclei (also known as the basal ganglia), which have two pathways that process information within the cerebrum. As shown in this video, the direct pathway is the shorter pathway through the system that results in increased activity in the cerebral cortex and increased motor activity. The direct pathway is described as resulting in disinhibition of the thalamus. What does disinhibition mean? What are the two neurons doing individually to cause this?

Watch this video to learn about the basal nuclei (also known as the basal ganglia), which have two pathways that process information within the cerebrum. As shown in this video, the indirect pathway is the longer pathway through the system that results in decreased activity in the cerebral cortex, and therefore less motor activity. The indirect pathway has an extra couple of connections in it, including disinhibition of the subthalamic nucleus. What is the end result on the thalamus, and therefore on movement initiated by the cerebral cortex?

There is a persistent myth that people are right-brained or left-brained, which is an oversimplification of an important concept about the cerebral hemispheres. There is some lateralization of function, in which the left side of the brain is devoted to language function and the right side is devoted to spatial and nonverbal reasoning. Whereas these functions are predominantly associated with those sides of the brain, there is no monopoly by either side on these functions. Many pervasive functions, such as language, are distributed globally around the cerebrum.

Some of the support for this misconception has come from studies of split brains. A drastic way to deal with a rare and devastating neurological condition (intractable epilepsy) is to separate the two hemispheres of the brain. After sectioning the corpus callosum, a split-brained patient will have trouble producing verbal responses on the basis of sensory information processed on the right side of the cerebrum, leading to the idea that the left side is responsible for language function.

However, there are well-documented cases of language functions lost from damage to the right side of the brain. The deficits seen in damage to the left side of the brain are classified as aphasia, a loss of speech function; damage on the right side can affect the use of language. Right-side damage can result in a loss of ability to understand figurative aspects of speech, such as jokes, irony, or metaphors. Nonverbal aspects of speech can be affected by damage to the right side, such as facial expression or body language, and right-side damage can lead to a flat affect in speech, or a loss of emotional expression in speechsounding like a robot when talking. Damage to language areas on the right side causes a condition called aprosodia where the patient has difficulty understanding or expressing the figurative part of speech.

The diencephalon is the one region of the adult brain that retains its name from embryologic development. The etymology of the word diencephalon translates to through brain. It is the connection between the cerebrum and the rest of the nervous system, with one exception. The rest of the brain, the spinal cord, and the PNS all send information to the cerebrum through the diencephalon. Output from the cerebrum passes through the diencephalon. The single exception is the system associated with olfaction, or the sense of smell, which connects directly with the cerebrum. In the earliest vertebrate species, the cerebrum was not much more than olfactory bulbs that received peripheral information about the chemical environment (to call it smell in these organisms is imprecise because they lived in the ocean).

The diencephalon is deep beneath the cerebrum and constitutes the walls of the third ventricle. The diencephalon can be described as any region of the brain with thalamus in its name. The two major regions of the diencephalon are the thalamus itself and the hypothalamus (Figure 14.3.8). There are other structures, such as the epithalamus, which contains the pineal gland, or the subthalamus, which includes the subthalamic nucleus that is part of the basal nuclei.

The thalamus is a collection of nuclei that relay information between the cerebral cortex and the periphery, spinal cord, or brain stem. All sensory information, except for the sense of smell, passes through the thalamus before processing by the cortex. Axons from the peripheral sensory organs, or intermediate nuclei, synapse in the thalamus, and thalamic neurons project directly to the cerebrum. It is a requisite synapse in any sensory pathway, except for olfaction. The thalamus does not just pass the information on, it also processes that information. For example, the portion of the thalamus that receives visual information will influence what visual stimuli are important, or what receives attention.

The cerebrum also sends information down to the thalamus, which usually communicates motor commands. This involves interactions with the cerebellum and other nuclei in the brain stem. The cerebrum interacts with the basal nuclei, which involves connections with the thalamus. The primary output of the basal nuclei is to the thalamus, which relays that output to the cerebral cortex. The cortex also sends information to the thalamus that will then influence the effects of the basal nuclei.

Inferior and slightly anterior to the thalamus is the hypothalamus, the other major region of the diencephalon. The hypothalamus is a collection of nuclei that are largely involved in regulating homeostasis. The hypothalamus is the executive region in charge of the autonomic nervous system and the endocrine system through its regulation of the anterior pituitary gland. Other parts of the hypothalamus are involved in memory and emotion as part of the limbic system.

The midbrain and the pons and medulla of the hindbrainare collectively referred to as the brain stem (Figure 14.3.9). The structure emerges from the ventral surface of the forebrain as a tapering cone that connects the brain to the spinal cord. Attached to the brain stem, but considered a separate region of the adult brain, is the cerebellum. The midbrain coordinates sensory representations of the visual, auditory, and somatosensory perceptual spaces. The pons is the main connection with the cerebellum. The pons and the medulla regulate several crucial functions, including the cardiovascular and respiratory systems.

The cranial nerves connect through the brain stem and provide the brain with the sensory input and motor output associated with the head and neck, including most of the special senses. The major ascending and descending pathways between the spinal cord and brain, specifically the cerebrum, pass through the brain stem.

One of the original regions of the embryonic brain, the midbrain is a small region between the thalamus and pons. It is separated into the tectum and tegmentum, from the Latin words for roof and floor, respectively. The cerebral aqueduct passes through the center of the midbrain, such that these regions are the roof and floor of that canal.

The tectum is composed of four bumps known as the colliculi (singular = colliculus), which means little hill in Latin. The inferior colliculus is the inferior pair of these enlargements and is part of the auditory brain stem pathway. Neurons of the inferior colliculus project to the thalamus, which then sends auditory information to the cerebrum for the conscious perception of sound. The superior colliculus is the superior pair and combines sensory information about visual space, auditory space, and somatosensory space. Activity in the superior colliculus is related to orienting the eyes to a sound or touch stimulus. If you are walking along the sidewalk on campus and you hear chirping, the superior colliculus coordinates that information with your awareness of the visual location of the tree right above you. That is the correlation of auditory and visual maps. If you suddenly feel something wet fall on your head, your superior colliculus integrates that with the auditory and visual maps and you know that the chirping bird just relieved itself on you. You want to look up to see the culprit, but do not.

The tegmentum is continuous with the gray matter of the rest of the brain stem. Throughout the midbrain, pons, and medulla, the tegmentum contains the nuclei that receive and send information through the cranial nerves, as well as regions that regulate important functions such as those of the cardiovascular and respiratory systems.

The word pons comes from the Latin word for bridge. It is visible on the anterior surface of the brain stem as the thick bundle of white matter attached to the cerebellum. The pons is the main connection between the cerebellum and the brain stem. The bridge-like white matter is only the anterior surface of the pons; the gray matter beneath that is a continuation of the tegmentum from the midbrain. Gray matter in the tegmentum region of the pons contains neurons receiving descending input from the forebrain that is sent to the cerebellum.

The medulla is the region known as the myelencephalon in the embryonic brain. The initial portion of the name, myel, refers to the significant white matter found in this regionespecially on its exterior, which is continuous with the white matter of the spinal cord. The tegmentum of the midbrain and pons continues into the medulla because this gray matter is responsible for processing cranial nerve information. A diffuse region of gray matter throughout the brain stem, known as the reticular formation, is related to sleep and wakefulness, such as general brain activity and attention.

The cerebellum, as the name suggests, is the little brain. It is covered in gyri and sulci like the cerebrum, and looks like a miniature version of that part of the brain (Figure 14.3.10). The cerebellum is largely responsible for comparing information from the cerebrum with sensory feedback from the periphery through the spinal cord. It accounts for approximately 10 percent of the mass of the brain.

Descending fibers from the cerebrum have branches that connect to neurons in the pons. Those neurons project into the cerebellum, providing a copy of motor commands sent to the spinal cord. Sensory information from the periphery, which enters through spinal or cranial nerves, is copied to a nucleus in the medulla known as the inferior olive. Fibers from this nucleus enter the cerebellum and are compared with the descending commands from the cerebrum. If the primary motor cortex of the frontal lobe sends a command down to the spinal cord to initiate walking, a copy of that instruction is sent to the cerebellum. Sensory feedback from the muscles and joints, proprioceptive information about the movements of walking, and sensations of balance are sent to the cerebellum through the inferior olive and the cerebellum compares them. If walking is not coordinated, perhaps because the ground is uneven or a strong wind is blowing, then the cerebellum sends out a corrective command to compensate for the difference between the original cortical command and the sensory feedback. The output of the cerebellum is into the midbrain, which then sends a descending input to the spinal cord to correct the messages going to skeletal muscles.

The description of the CNS is concentrated on the structures of the brain, but the spinal cord is another major organ of the system. Whereas the brain develops out of expansions of the neural tube into primary and then secondary vesicles, the spinal cord maintains the tube structure and is only specialized into certain regions. As the spinal cord continues to develop in the newborn, anatomical features mark its surface. The anterior midline is marked by the anterior median fissure, and the posterior midline is marked by the posterior median sulcus. Axons enter the posterior side through the dorsal (posterior) nerve root, which marks the posterolateral sulcus on either side. The axons emerging from the anterior side do so through the ventral (anterior) nerve root. Note that it is common to see the terms dorsal (dorsal = back) and ventral (ventral = belly) used interchangeably with posterior and anterior, particularly in reference to nerves and the structures of the spinal cord. You should learn to be comfortable with both.

On the whole, the posterior regions are responsible for sensory functions and the anterior regions are associated with motor functions. This comes from the initial development of the spinal cord, which is divided into the basal plate and the alar plate. The basal plate is closest to the ventral midline of the neural tube, which will become the anterior face of the spinal cord and gives rise to motor neurons. The alar plate is on the dorsal side of the neural tube and gives rise to neurons that will receive sensory input from the periphery.

The length of the spinal cord is divided into regions that correspond to the regions of the vertebral column. The name of a spinal cord region corresponds to the level at which spinal nerves pass through the intervertebral foramina. Immediately adjacent to the brain stem is the cervical region, followed by the thoracic, then the lumbar, and finally the sacral region. The spinal cord is not the full length of the vertebral column because the spinal cord does not grow significantly longer after the first or second year, but the skeleton continues to grow. The nerves that emerge from the spinal cord pass through the intervertebral formina at the respective levels. As the vertebral column grows, these nerves grow with it and result in a long bundle of nerves that resembles a horses tail and is named the cauda equina. The sacral spinal cord is at the level of the upper lumbar vertebral bones. The spinal nerves extend from their various levels to the proper level of the vertebral column.

In cross-section, the gray matter of the spinal cord has the appearance of an ink-blot test, with the spread of the gray matter on one side replicated on the othera shape reminiscent of a bulbous capital H. As shown in Figure 14.3.11, the gray matter is subdivided into regions that are referred to as horns. The posterior horn is responsible for sensory processing. The anterior horn sends out motor signals to the skeletal muscles. The lateral horn, which is only found in the thoracic, upper lumbar, and sacral regions, is the central component of the sympathetic division of the autonomic nervous system.

Some of the largest neurons of the spinal cord are the multipolar motor neurons in the anterior horn. The fibers that cause contraction of skeletal muscles are the axons of these neurons. The motor neuron that causes contraction of the big toe, for example, is located in the sacral spinal cord. The axon that has to reach all the way to the belly of that muscle may be a meter in length. The neuronal cell body that maintains that long fiber must be quite large, possibly several hundred micrometers in diameter, making it one of the largest cells in the body.

Just as the gray matter is separated into horns, the white matter of the spinal cord is separated into columns. Ascending tracts of nervous system fibers in these columns carry sensory information up to the brain, whereas descending tracts carry motor commands from the brain. Looking at the spinal cord longitudinally, the columns extend along its length as continuous bands of white matter. Between the two posterior horns of gray matter are the posterior columns. Between the two anterior horns, and bounded by the axons of motor neurons emerging from that gray matter area, are the anterior columns. The white matter on either side of the spinal cord, between the posterior horn and the axons of the anterior horn neurons, are the lateral columns. The posterior columns are composed of axons of ascending tracts. The anterior and lateral columns are composed of many different groups of axons of both ascending and descending tractsthe latter carrying motor commands down from the brain to the spinal cord to control output to the periphery.

Watch this video to learn about the gray matter of the spinal cord that receives input from fibers of the dorsal (posterior) root and sends information out through the fibers of the ventral (anterior) root. As discussed in this video, these connections represent the interactions of the CNS with peripheral structures for both sensory and motor functions. The cervical and lumbar spinal cords have enlargements as a result of larger populations of neurons. What are these enlargements responsible for?

Parkinsons disease is neurodegenerative, meaning that neurons die that cannot be replaced, so there is no cure for the disorder. Treatments for Parkinsons disease are aimed at increasing dopamine levels in the striatum. Currently, the most common way of doing that is by providing the amino acid L-DOPA, which is a precursor to the neurotransmitter dopamine and can cross the blood-brain barrier. With levels of the precursor elevated, the remaining cells of the substantia nigra pars compacta can make more neurotransmitter and have a greater effect. Unfortunately, the patient will become less responsive to L-DOPA treatment as time progresses, and it can cause increased dopamine levels elsewhere in the brain, which are associated with psychosis or schizophrenia.

Visit this site for a thorough explanation of Parkinsons disease.

Compared with the nearest evolutionary relative, the chimpanzee, the human has a brain that is huge. At a point in the past, a common ancestor gave rise to the two species of humans and chimpanzees. That evolutionary history is long and is still an area of intense study. But something happened to increase the size of the human brain relative to the chimpanzee. Read this article in which the author explores the current understanding of why this happened.

According to one hypothesis about the expansion of brain size, what tissue might have been sacrificed so energy was available to grow our larger brain? Based on what you know about that tissue and nervous tissue, why would there be a trade-off between them in terms of energy use?

Have you ever heard the claim that humans only use 10 percent of their brains? Maybe you have seen an advertisement on a website saying that there is a secret to unlocking the full potential of your mindas if there were 90 percent of your brain sitting idle, just waiting for you to use it. If you see an ad like that, dont click. It isnt true.

An easy way to see how much of the brain a person uses is to take measurements of brain activity while performing a task. An example of this kind of measurement is functional magnetic resonance imaging (fMRI), which generates a map of the most active areas and can be generated and presented in three dimensions (Figure 14.3.12). This procedure is different from the standard MRI technique because it is measuring changes in the tissue in time with an experimental condition or event.

The underlying assumption is that active nervous tissue will have greater blood flow. By having the subject perform a visual task, activity all over the brain can be measured. Consider this possible experiment: the subject is told to look at a screen with a black dot in the middle (a fixation point). A photograph of a face is projected on the screen away from the center. The subject has to look at the photograph and decipher what it is. The subject has been instructed to push a button if the photograph is of someone they recognize. The photograph might be of a celebrity, so the subject would press the button, or it might be of a random person unknown to the subject, so the subject would not press the button.

In this task, visual sensory areas would be active, integrating areas would be active, motor areas responsible for moving the eyes would be active, and motor areas for pressing the button with a finger would be active. Those areas are distributed all around the brain and the fMRI images would show activity in more than just 10 percent of the brain (some evidence suggests that about 80 percent of the brain is using energybased on blood flow to the tissueduring well-defined tasks similar to the one suggested above). This task does not even include all of the functions the brain performs. There is no language response, the body is mostly lying still in the MRI machine, and it does not consider the autonomic functions that would be ongoing in the background.

Considering the anatomical regions of the nervous system, there are specific names for the structures within each division. A localized collection of neuron cell bodies is referred to as a nucleus in the CNS and as a ganglion in the PNS. A bundle of axons is referred to as a tract in the CNS and as a nerve in the PNS. Whereas nuclei and ganglia are specifically in the central or peripheral divisions, axons can cross the boundary between the two. A single axon can be part of a nerve and a tract. The name for that specific structure depends on its location.

Nervous tissue can also be described as gray matter and white matter on the basis of its appearance in unstained tissue. These descriptions are more often used in the CNS. Gray matter is where nuclei are found and white matter is where tracts are found. In the PNS, ganglia are basically gray matter and nerves are white matter.

The adult brain is separated into four major regions: the cerebrum, the diencephalon, the brain stem, and the cerebellum. The cerebrum is the largest portion and contains the cerebral cortex and subcortical nuclei. It is divided into two halves by the longitudinal fissure.

The cortex is separated into the frontal, parietal, temporal, and occipital lobes. The frontal lobe is responsible for motor functions, from planning movements through executing commands to be sent to the spinal cord and periphery. The most anterior portion of the frontal lobe is the prefrontal cortex, which is associated with aspects of personality through its influence on motor responses in decision-making.

The other lobes are responsible for sensory functions. The parietal lobe is where somatosensation is processed. The occipital lobe is where visual processing begins, although the other parts of the brain can contribute to visual function. The temporal lobe contains the cortical area for auditory processing, but also has regions crucial for memory formation.

Nuclei beneath the cerebral cortex, known as the subcortical nuclei, are responsible for augmenting cortical functions. The basal nuclei receive input from cortical areas and compare it with the general state of the individual through the activity of a dopamine-releasing nucleus. The output influences the activity of part of the thalamus that can then increase or decrease cortical activity that often results in changes to motor commands. The basal forebrain is responsible for modulating cortical activity in attention and memory. The limbic system includes deep cerebral nuclei that are responsible for emotion and memory.

The diencephalon includes the thalamus and the hypothalamus, along with some other structures. The thalamus is a relay between the cerebrum and the rest of the nervous system. The hypothalamus coordinates homeostatic functions through the autonomic and endocrine systems.

The brain stem is composed of the midbrain, pons, and medulla. It controls the head and neck region of the body through the cranial nerves. There are control centers in the brain stem that regulate the cardiovascular and respiratory systems.

The cerebellum is connected to the brain stem, primarily at the pons, where it receives a copy of the descending input from the cerebrum to the spinal cord. It can compare this with sensory feedback input through the medulla and send output through the midbrain that can correct motor commands for coordination.

Both cells are inhibitory. The first cell inhibits the second one. Therefore, the second cell can no longer inhibit its target. This is disinhibition of that target across two synapses.

Watch this video to learn about the basal nuclei (also known as the basal ganglia), which have two pathways that process information within the cerebrum. As shown in this video, the indirect pathway is the longer pathway through the system that results in decreased activity in the cerebral cortex, and therefore less motor activity. The indirect pathway has an extra couple of connections in it, including disinhibition of the subthalamic nucleus. What is the end result on the thalamus, and therefore on movement initiated by the cerebral cortex?

By disinhibiting the subthalamic nucleus, the indirect pathway increases excitation of the globus pallidus internal segment. That, in turn, inhibits the thalamus, which is the opposite effect of the direct pathway that disinhibits the thalamus.

There are more motor neurons in the anterior horns that are responsible for movement in the limbs. The cervical enlargement is for the arms, and the lumbar enlargement is for the legs.

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14.3 The Brain and Spinal Cord Anatomy & Physiology

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January 3rd, 2023

Stem Cell Therapy for Spinal Cord Injury – PubMed

By daniellenierenberg

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

Keywords: AD-MSCs; BM-MSCs; ESCs; EVs; NPCs; NSCs; U-MSCs; iPSCs; spinal cord injury; stem cells.

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January 3rd, 2023

Spinal cord injury – Diagnosis and treatment – Mayo Clinic

By daniellenierenberg

Diagnosis

In the emergency room, a doctor may be able to rule out a spinal cord injury by examination, testing for sensory function and movement, and by asking some questions about the accident.

But if the injured person complains of neck pain, isn't fully awake, or has obvious signs of weakness or neurological injury, emergency diagnostic tests may be needed.

These tests can include:

A few days after injury, when some of the swelling might have subsided, your doctor will conduct a more comprehensive neurological exam to determine the level and completeness of your injury. This involves testing your muscle strength and your ability to sense light touch and pinprick sensations.

Unfortunately, there's no way to reverse damage to the spinal cord. But researchers are continually working on new treatments, including prostheses and medications, that might promote nerve cell regeneration or improve the function of the nerves that remain after a spinal cord injury.

In the meantime, spinal cord injury treatment focuses on preventing further injury and empowering people with a spinal cord injury to return to an active and productive life.

Urgent medical attention is critical to minimize the effects of head or neck trauma. Therefore, treatment for a spinal cord injury often begins at the accident scene.

Emergency personnel typically immobilize the spine as gently and quickly as possible using a rigid neck collar and a rigid carrying board, which they use during transport to the hospital.

In the emergency room, doctors focus on:

If you have a spinal cord injury, you'll usually be admitted to the intensive care unit for treatment. You might be transferred to a regional spine injury center that has a team of neurosurgeons, orthopedic surgeons, spinal cord medicine specialists, psychologists, nurses, therapists and social workers with expertise in spinal cord injury.

Medications. Methylprednisolone (Solu-Medrol) given through a vein in the arm (IV) has been used as a treatment option for an acute spinal cord injury in the past. But recent research has shown that the potential side effects, such as blood clots and pneumonia, from using this medication outweigh the benefits.

Because of this, methylprednisolone is no longer recommended for routine use after a spinal cord injury.

After the initial injury or condition stabilizes, doctors turn their attention to preventing secondary problems that may arise, such as deconditioning, muscle contractures, pressure ulcers, bowel and bladder issues, respiratory infections, and blood clots.

The length of your hospital stay will depend on your condition and the medical issues you face. Once you're well enough to participate in therapies and treatment, you might transfer to a rehabilitation facility.

Rehabilitation team members will begin to work with you while you're in the early stages of recovery. Your team might include a physical therapist, an occupational therapist, a rehabilitation nurse, a rehabilitation psychologist, a social worker, a dietitian, a recreation therapist, and a doctor who specializes in physical medicine (physiatrist) or spinal cord injuries.

During the initial stages of rehabilitation, therapists usually emphasize maintaining and strengthening muscle function, redeveloping fine motor skills, and learning ways to adapt to do day-to-day tasks.

You'll be educated on the effects of a spinal cord injury and how to prevent complications, and you'll be given advice on rebuilding your life and increasing your quality of life and independence.

You'll be taught many new skills, and you'll use equipment and technologies that can help you live on your own as much as possible. You'll be encouraged to resume your favorite hobbies, participate in social and fitness activities, and return to school or the workplace.

Medications might be used to manage some of the effects of spinal cord injury. These include medications to control pain and muscle spasticity, as well as medications that can improve bladder control, bowel control and sexual functioning.

Inventive medical devices can help people with a spinal cord injury become more independent and more mobile. These include:

Your doctor might not be able to give you a prognosis right away. Recovery, if it occurs, usually relates to the severity and level of the injury. The fastest rate of recovery is often seen in the first six months, but some people make small improvements for up to 1 to 2 years.

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

An accident that results in paralysis is a life-changing event. Suddenly having a disability can be frightening and confusing, and adapting is no easy task. You'll likely wonder how your spinal cord injury will affect your everyday activities, job, relationships and long-term happiness.

Recovery takes time, but many people who are paralyzed progress to lead productive and fulfilling lives. It's essential to stay motivated and get the support you need.

If you're newly injured, you and your family will likely experience a period of mourning. The grieving process, which is a normal, healthy part of your recovery, is different for everyone.

It's natural and important to grieve the loss of the way you were. But it's also necessary to set new goals and find ways to go forward.

You'll probably have concerns about how your injury will affect your lifestyle, your financial situation and your relationships. Grieving and emotional stress are normal and common.

However, if your grief is affecting your care, causing you to isolate yourself or prompting you to abuse alcohol or other drugs, you might want to talk to a social worker, psychologist or psychiatrist. Or you might find it helpful to join a support group of people with spinal cord injuries.

Talking with others who understand what you're going through can be encouraging, and you might find good advice on adapting areas of your home or work space to better meet your needs. Ask your doctor or rehabilitation specialist if there are support groups in your area.

One of the best ways to regain control of your life is to educate yourself about your injury and your options for gaining more independence. A range of driving equipment and vehicle modifications is available today.

The same is true of home modification products. Ramps, wider doors, special sinks, grab bars and easy-to-turn doorknobs make it possible for you to live more autonomously.

The costs of a spinal cord injury can be overwhelming, but you might be eligible for economic assistance or support services from the state or federal government or from charitable organizations. Your rehabilitation team can help you identify resources in your area.

Some friends and family members might be unsure about how to act around you. Being educated about your spinal cord injury and willing to educate others can benefit all of you.

Explain the effects of your injury and what others can do to help. But don't hesitate to tell friends and loved ones when they're helping too much. Although it may be uncomfortable at first, talking about your injury can strengthen your relationships with family and friends.

Your spinal cord injury might affect your body's sexual responsiveness. However, you're a sexual being with sexual desires. A fulfilling emotional and physical relationship is possible but requires communication, experimentation and patience.

A professional counselor can help you and your partner communicate your needs and feelings. Your doctor can provide the medical information you need regarding sexual health. You can have a satisfying future complete with intimacy and sexual pleasure.

As you learn more about your injury and treatment options, you might be surprised by all you can do. Thanks to new technologies, treatments and devices, people with spinal cord injuries play basketball and participate in track meets. They paint and take photographs. They get married, have and raise children, and have rewarding jobs.

Advances in stem cell research and nerve cell regeneration give hope for greater recovery for people with spinal cord injuries. And new treatments are being investigated for people with long-standing spinal cord injuries.

No one knows when new treatments will be available, but you can remain hopeful about the future of spinal cord research while living your life to the fullest today.

Traumatic spinal cord injuries are emergencies, and people who are injured might not be able to participate in their care at first.

A number of specialists will be involved in stabilizing the condition, including a doctor who specializes in nervous system disorders (neurologist) and a surgeon who specializes in spinal cord injuries and other nervous system problems (neurosurgeon), among others.

A doctor who specializes in spinal cord injuries will lead your rehabilitation team, which will include a variety of specialists.

If you have a possible spinal cord injury or you accompany someone who's had a spinal cord injury and can't provide the necessary information, here are some things you can do.

For a spinal cord injury, some basic questions to ask the doctor include:

Don't hesitate to ask other questions you have.

Your doctor is likely to ask questions, including:

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December 25th, 2022

Spinal Cord Injury: Hope Through Research | National Institute of …

By daniellenierenberg

What is a spinal cord injury?What are some signs and symptoms of spinal cord injury?How are spinal cord injuries diagnosed?How is SCI treated?What research is being done?How can I help with research?Where can I get more information?Appendix

A spinal cord injury (SCI) is damage to the tight bundle of cells and nerves that sends and receives signals from the brain to and from the rest of the body. The spinal cord extends from the lower part of the brain down through the lower back.

SCI can be caused by direct injury to the spinal cord itself or from damage to the tissue and bones (vertebrae) that surround the spinal cord. This damage can result in temporary or permanent changes in sensation, movement, strength, and body functions below the site of injury.

Injury and severity

The extent of disability depends on where along the spinal cord the injury occurs and the severity of the injury.

Loss of nerve function occurs below the level of injury. An injury higher on the spinal cord can cause paralysis in most of the body and affect all limbs (called tetraplegia or quadriplegia). A lower injury to the spinal cord may cause paralysis affecting the legs and lower body (called paraplegia).

A spinal cord injury can damage a few, many, or almost all of the nerve fibers that cross the site of injury. A variety of cells located in and around the injury site may also die. Some injuries having little or no nerve cell death may allow an almost complete recovery.

Type of injury

A spinal cord injury can be classified as complete or incomplete.

Primary damage is immediate and is caused directly by the injury. Secondary damage results from inflammation and swelling that can press on the spinal cord and vertebrae, as well as from changes in the activity of cells and cell death.

Common causes

Motor vehicle accidents and catastrophic falls are the most common causes of SCI in the United States. The rest are due to acts of violence (primarily gunshot wounds and assaults), sports injuries, medical or surgical injury, industrial accidents, diseases and conditions that can damage the spinal cord, and other less common causes.

For information on what makes up the spinal cord and spinal column, see the Appendix at the end of this document.

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A spinal cord injury can cause one or more symptoms including:

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How are spinal cord injuries diagnosed?

The emergency room physician will check for movement or sensation at or below the level of injury, as well as proper breathing, responsiveness, and weakness. Emergency medical tests for a spinal cord injury include:

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Immediate (acute) treatment

At the accident scene, emergency personnel will put a rigid collar around the neck and carefully place the person on a rigid backboard to prevent further damage to the spinal cord. Sometimes the person may be sedated to relax and prevent movement. A breathing tube may be inserted if the person has problems breathing and the body isnt receiving enough oxygen from the lungs.

Immediate treatment at the trauma center may include:

Possible Complications of SCI and treatment

Once someone has survived the injury and begins to cope psychologically and emotionally, the next concern is how to live with disabilities. Doctors are now able to predict with reasonable accuracy the likely long-term outcome of spinal cord injuries. This helps people experiencing SCI set achievable goals for themselves and gives families and loved ones a realistic set of expectations for the future.

Rehabilitation

Rehabilitation programs combine physical therapies with skill-building activities and counseling to provide social and emotional support, as well as to increase independence and quality of life.

A rehabilitation team is usually led by a doctor specializing in physical medicine and rehabilitation (called a physiatrist) and often includes social workers, physical and occupational therapists, recreational therapists, rehabilitation nurses, rehabilitation psychologists, vocational counselors, nutritionists, a case worker, and other specialists.

In the initial phase of rehabilitation, therapists emphasize regaining communication skills and leg and arm strength. For some individuals, mobility will only be possible with assistive devices such as a walker, leg braces, or a wheelchair. Communication skills such as writing, typing, and using the telephone may also require adaptive devices for some people with tetraplegia.

Adaptive devices also may help people with spinal cord injury to regain independence and improve mobility and quality of life. Such devices may include a wheelchair, electronic stimulators, assisted training with walking,neural prostheses (assistive devices that may stimulate the nerves to restore lost functions), computer adaptations, and other computer-assisted technology.

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Scientists continue to investigate new ways to better understand and treat spinal cord injuries.

Much of this research is conducted or funded by the National Institute of Neurological Disorders and Stroke (NINDS). NINDS is a component of the National Institutes of Health (NIH), the leading supporter of biomedical research in the world. Other NIH components, as well as the Department of Veterans Affairs, other Federal agencies, research institutions, and voluntary health organizations, also fund and conduct basic to clinical research related to improvement of function in paralyzed individuals.

The Brain Research through Advancing Innovative Technologies (BRAIN) Initiative brings together multiple federal agencies and private organizations to develop and apply new technologies to understand how complex circuits of nerve cells enable thinking, movement control, and perception. Research funded as part of the BRAIN Initiative that has the potential to improve the outlook for SCI includes:

Basic spinal cord function research studies how the normal spinal cord develops, processes sensory information, controls movement, and generates rhythmic patterns (like walking and breathing). Basic studies using cells and animal models provide an essential foundation for developing interventions for spinal cord injury.

Research on injury mechanisms focuses on what causes immediate harm and on the cascade of helpful and harmful bodily reactions that protect from or contribute to damage in the hours and days following a spinal cord injury. This includes testing of neuroprotective interventions in laboratory animals.

Current research on SCI is focused on advancing our understanding of four key principles of spinal cord repair:

Neural engineering strategies build on decades of pioneering NINDS investment that established the field of neural prostheses. For example, researchers are developing a networked functional electrical stimulation system to restore independence through combined implants for hand function, postural control, and bowel and bladder control. NINDS has also led development of experimental brain computer interfaces that enable people to control a computer cursor or robotic arm directly from their brains.

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Clinical research uses human volunteersboth those who are healthy or may have an illness or diseaseto help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease. For information about finding and participating in clinical research visit NIH Clinical Research Trials and You at http://www.nih.gov/health/clinicaltrials. Use search terms such as spinal cord injury and tetraplegia to access current and completed trials involving spinal injury.

Other centers maintain registries of people interested in participating in ongoing or future clinical research studies. A multi-site network supported by the Christopher and Dana Reeve Foundation called the NeuroRecovery Network also accepts volunteer research participants. For more information, see http://www.christopherreeve.org/site/c.ddJFKRNoFiG/b.5399929/k.6F37/NeuroRecovery_Network.htm.

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For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAINP.O. Box 5801Bethesda, MD 20824800-352-9424

Information also is available from the following organizations:

Christopher and Dana Reeve Foundation Email: Information@christopherreeve.org 973-379-2690 or 800-225-0292

Miami Project to Cure ParalysisEmail: miamiproject@miami.edu 305-243-6001 or 800-782-6387

National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) 202-401-4634; 202-245-7316 (TTY)

National Rehabilitation Information Center (NARIC) Landover, MD 20785301-459-5900; 800-346-2742; 301-459-5984 (TTY)

Paralyzed Veterans of America (PVA) Email: info@pva.orr 800-424-8200

United Spinal Association Email: askus@unitedspinal.org 718-803-3782 or 800-962-9629

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Anatomy of the spinal cord

The spinal cord is a soft, cylindrical column of tightly bundled nerve cells (neurons and glia), nerve fibers that transmit nerve signals (called axons), and blood vessels. It sends and receives information between the brain and the rest of the body. Millions of nerve cells situated in the spinal cord itself also coordinate complex patterns of movements such as rhythmic breathing and walking.

The spinal cord extends from the brain to the lower back through a canal in the center of the bones of the spine. Like the brain, the spinal cord is protected by three layers of tissue and is surrounded by the cerebrospinal fluid that acts as a cushion against shock or injury.

Inside the spinal cord is:

Other types of nerve cells sit just outside the spinal cord and relay information to the brain.

31 pairs of nerves, each of which contains thousands of axons, are divided into 4 regions having individual segments and link the spinal cord to muscles and other parts of the body:

The spinal column, which surrounds and protects the spinal cord, is made up of 33 rings of bone (called vertebrae), pads of semi-rigid cartilage (called discs), and narrow spaces called foramen that act as passages for spinal nerves to travel to and from the rest of the body. These are places where the spinal cord is particularly vulnerable to direct injury.

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"Spinal Cord Injury: Hope Through Research", NINDS, Publication date July 2013.

NIH Publication 13-NS-160

Back toSpinal Cord Injury Information Page

See a list of all NINDS Disorders

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Lesin de la Mdula Espinal

Prepared by:Office of Communications and Public LiaisonNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

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December 1st, 2022

Stem cell controversy – Wikipedia

By daniellenierenberg

Ethical controversy over the use of embryonic stem cells

The stem cell controversy is the consideration of the ethics of research involving the development and use of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves human embryos. For example, adult stem cells, amniotic stem cells, and induced pluripotent stem cells do not involve creating, using, or destroying human embryos, and thus are minimally, if at all, controversial. Many less controversial sources of acquiring stem cells include using cells from the umbilical cord, breast milk, and bone marrow, which are not pluripotent.

For many decades, stem cells have played an important role in medical research, beginning in 1868 when Ernst Haeckel first used the phrase to describe the fertilized egg which eventually gestates into an organism. The term was later used in 1886 by William Sedgwick to describe the parts of a plant that grow and regenerate. Further work by Alexander Maximow and Leroy Stevens introduced the concept that stem cells are pluripotent. This significant discovery led to the first human bone marrow transplant by E. Donnall Thomas in 1956, which although successful in saving lives, has generated much controversy since. This has included the many complications inherent in stem cell transplantation (almost 200 allogeneic marrow transplants were performed in humans, with no long-term successes before the first successful treatment was made), through to more modern problems, such as how many cells are sufficient for engraftment of various types of hematopoietic stem cell transplants, whether older patients should undergo transplant therapy, and the role of irradiation-based therapies in preparation for transplantation.

The discovery of adult stem cells led scientists to develop an interest in the role of embryonic stem cells, and in separate studies in 1981 Gail Martin and Martin Evans derived pluripotent stem cells from the embryos of mice for the first time. This paved the way for Mario Capecchi, Martin Evans, and Oliver Smithies to create the first knockout mouse, ushering in a whole new era of research on human disease. In 1995 adult stem cell research with human use was patented (US PTO with effect from 1995). In fact, human use was published in World J Surg 1991 & 1999 (B G Matapurkar). Salhan, Sudha (August 2011).[1]

In 1998, James Thomson and Jeffrey Jones derived the first human embryonic stem cells, with even greater potential for drug discovery and therapeutic transplantation. However, the use of the technique on human embryos led to more widespread controversy as criticism of the technique now began from the wider public who debated the moral ethics of questions concerning research involving human embryonic cells.

Since pluripotent stem cells have the ability to differentiate into any type of cell, they are used in the development of medical treatments for a wide range of conditions.[2] Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed due to their ability to repair extensive tissue damage.[3]

Great levels of success and potential have been realized from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Only cells from an embryo at the morula stage or earlier are truly totipotent, meaning that they are able to form all cell types including placental cells. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become.

Destruction of a human embryo is required in order to research new embryonic cell lines. Much of the debate surrounding human embryonic stem cells, therefore, concern ethical and legal quandaries around the destruction of an embryo. Ethical and legal questions such as "At what point does one consider life to begin?" and "Is it just to destroy a human embryo if it has the potential to cure countless numbers of patients and further our understanding of disease?" are central to the controversy. Political leaders debate how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged.[4]

Much of the criticism has been a result of religious beliefs and, in the most high-profile case, US President George W Bush signed an executive order banning the use of federal funding for any stem cell lines other than those already in existence, stating at the time, "My position on these issues is shaped by deeply held beliefs," and "I also believe human life is a sacred gift from our creator."[5] This ban was in part revoked by his successor Barack Obama, who stated: "As a person of faith, I believe we are called to care for each other and work to ease human suffering. I believe we have been given the capacity and will to pursue this research and the humanity and conscience to do so responsibly."[6]

Some stem cell researchers are working to develop techniques of isolating stem cells with similar potency as embryonic stem cells, but do not require the destruction of a human embryo.

Foremost among these was the discovery in August 2006 that human adult somatic cells can be cultured in vitro with the four Yamanaka factors (Oct-4, SOX2, c-Myc, KLF4) which effectively returns a cell to the pluripotent state similar to that observed in embryonic stem cells.[7][8] This major breakthrough won a Nobel Prize for the discoverers, Shinya Yamanaka and John Gurdon.[9] Induced pluripotent stem cells are those derived from adult somatic cells and have the potential to provide an alternative for stem cell research that does not require the destruction of human embryos. Some debate remains about the similarities of these cells to embryonic stem cells as research has shown that the induced pluripotent cells may have a different epigenetic memory or modifications to the genome than embryonic stem cells depending on the tissue of origin and donor the iPSCs come from.[10] While this may be the case, epigenetic manipulation of the cells is possible using small molecules and more importantly, iPSCs from multiple tissues of origin have been shown to give rise to a viable organism similar to the way ESCs can.[11] This allows iPSCs to serve as a powerful tool for tissue generation, drug screening, disease modeling, and personalized medicine that has far fewer ethical considerations than embryonic stem cells that would otherwise serve the same purpose.

In an alternative technique, researchers at Harvard University, led by Kevin Eggan and Savitri Marajh, have transferred the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[12] This technique known as somatic cell nuclear transfer (SCNT) creates pluripotent cells that are genetically identical to the donor.[13] While the creation of stem cells via SCNT does not destroy an embryo, it requires an oocyte from a donor which opens the door to a whole new set of ethical considerations such as the debate as to whether or not it is appropriate to offer financial incentives to female donors.[14]

Researchers at Advanced Cell Technology, led by Robert Lanza and Travis Wahl, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[15] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[16] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos.[17]"These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[18]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when used correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells." The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs, as well."[19] AFSCs have been found to express both embryonic and adult stem cell markers as well as having the ability to be maintained over 250 population doublings.[20]

Similarly, pro-life supporters claim that the use of adult stem cells from sources such as the cord blood has consistently produced more promising results than the use of embryonic stem cells.[21] Research has shown that umbilical cord blood (UCB) is in fact a viable source for stem cells and their progenitors which occur in high frequencies within the fluid. Furthermore, these cells may hold an advantage over induced PSC as they can create large quantities of homogenous cells.[22]

IPSCs and other embryonic stem cell alternatives must still be collected and maintained with the informed consent of the donor as a donor's genetic information is still within the cells and by the definition of pluripotency, each alternative cell type has the potential to give rise to viable organisms. Generation of viable offspring using iPSCs has been shown in mouse models through tetraploid complementation.[23][24] This potential for the generation of viable organisms and the fact that iPSC cells contain the DNA of donors require that they be handled along the ethical guidelines laid out by the food and drug administration (FDA), European Medicines Agency (EMA), and International Society for Stem Cell Research (ISSCR).

Stem cell debates have motivated and reinvigorated the anti-abortion movement, whose members are concerned with the rights and status of the human embryo as an early-aged human life. They believe that embryonic stem cell research profits from and violates the sanctity of life and is tantamount to murder.[25] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell. The view of those in favor is that these embryos would otherwise be discarded, and if used as stem cells, they can survive as a part of a living human person.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, an estimated at least 400,000 such embryos exist.[26] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[27] See also embryo donation.

Medical researchers widely report that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson's disease are two examples that have been championed by high-profile media personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health's Guidelines stated:

... research involving human pluripotent stem cells ... promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson's disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards.[28]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.[29] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost-effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before noncancerous stem cells can be created.[30][31][32][33]

Update of article to include 2009/2010 current stem cell usages in clinical trials:[34][35] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those who have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

This is usually presented as a counter-argument to using adult stem cells, as an alternative that does not involve embryonic destruction.

Adult stem cells have provided many different therapies for illnesses such as Parkinson's disease, leukemia, multiple sclerosis, lupus, sickle-cell anemia, and heart damage[43] (to date, embryonic stem cells have also been used in treatment),[44] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.[45] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

Austria, Denmark, France, Germany, Portugal and Ireland do not allow the production of embryonic stem cell lines,[46] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, and the United Kingdom.[46]

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos. In 1995, the NIH Human Embryo Research Panel advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[47] but did agree to fund research on leftover embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed the 1995 DickeyWicker Amendment (the final bill, which included the Dickey-Wicker Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of human embryonic stem cells (hESC).[48] This prompted the Clinton administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president's National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case[49][50][51][52]), the Clinton administration had decided that it would be permissible under the Dickey-Wicker Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001, that federal funds, for the first time, would be made available for hESC research on currently existing embryonic stem cell lines. President Bush authorized research on existing human embryonic stem cell lines, not on human embryos under a specific, unrealistic timeline in which the stem cell lines must have been developed. However, the Bush Administration chose not to permit taxpayer funding for research on hESC cell lines not currently in existence, thus limiting federal funding to research in which "the life-and-death decision has already been made."[53] The Bush Administration's guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.

In April 2004, 206 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238194 to loosen the limitations on federally funded embryonic stem-cell research by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors despite Bush's promise to veto the bill if passed.[54] On July 29, 2005, Senate Majority Leader William H. Frist (R-TN) announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[55] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (the Stem Cell Research Enhancement Act) 6337, which would have made it legal for the federal government to spend federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures.[56] On July 19, 2006, President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

In 2005 and 2007, Congressman Ron Paul introduced the Cures Can Be Found Act,[57] with 10 cosponsors. With an income tax credit, the bill favors research upon non-embryonic stem cells obtained from placentas, umbilical cord blood, amniotic fluid, humans after birth, or unborn human offspring who died of natural causes; the bill was referred to committee. Paul argued that hESC research is outside of federal jurisdiction either to ban or to subsidize.[58]

Bush vetoed another bill, the Stem Cell Research Enhancement Act of 2007,[59] which would have amended the Public Health Service Act to provide for human embryonic stem cell research. The bill passed the Senate on April 11 by a vote of 6334, then passed the House on June 7 by a vote of 247176. President Bush vetoed the bill on July 19, 2007.[60]

On March 9, 2009, President Obama removed the restriction on federal funding for newer stem cell lines.[61] Two days after Obama removed the restriction, the president then signed the Omnibus Appropriations Act of 2009, which still contained the long-standing DickeyWicker Amendment which bans federal funding of "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death;"[62] the Congressional provision effectively prevents federal funding being used to create new stem cell lines by many of the known methods. So, while scientists might not be free to create new lines with federal funding, President Obama's policy allows the potential of applying for such funding into research involving the hundreds of existing stem cell lines as well as any further lines created using private funds or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a significant expansion of options over the limits imposed by President Bush, who restricted funding to the 21 viable stem cell lines that were created before he announced his decision in 2001.[63]The ethical concerns raised during Clinton's time in office continue to restrict hESC research and dozens of stem cell lines have been excluded from funding, now by judgment of an administrative office rather than presidential or legislative discretion.[64]

In 2005, the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[65] Sigrid Fry-Revere has argued that private organizations, not the federal government, should provide funding for stem-cell research, so that shifts in public opinion and government policy would not bring valuable scientific research to a grinding halt.[66]

In 2005, the State of California took out $3 billion in bond loans to fund embryonic stem cell research in that state.[67]

China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning.[68]

Generally speaking, no group advocates for unrestricted stem cell research, especially in the context of embryonic stem cell research.

According to Rabbi Levi Yitzchak Halperin of the Institute for Science and Jewish Law in Jerusalem, embryonic stem cell research is permitted so long as it has not been implanted in the womb. Not only is it permitted, but research is encouraged, rather than wasting it.

As long as it has not been implanted in the womb and it is still a frozen fertilized egg, it does not have the status of an embryo at all and there is no prohibition to destroy it...

However in order to remove all doubt [as to the permissibility of destroying it], it is preferable not to destroy the pre-embryo unless it will otherwise not be implanted in the woman who gave the eggs (either because there are many fertilized eggs, or because one of the parties refuses to go on with the procedure the husband or wife or for any other reason). Certainly it should not be implanted into another woman.... The best and worthiest solution is to use it for life-saving purposes, such as for the treatment of people that suffered trauma to their nervous system, etc.

Rabbi Levi Yitzchak Halperin, Ma'aseh Choshev vol. 3, 2:6

Similarly, the sole Jewish majority state, Israel, permits research on embryonic stem cells.

The Catholic Church opposes human embryonic stem cell research calling it "an absolutely unacceptable act." The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it "involves no harm to human beings at any state of development."[69] This support has been expressed both politically and financially, with different Catholic groups either raising money indirectly, offering grants, or seeking to pass federal legislation, according to the United States Conference of Catholic Bishops. Specific examples include a grant from the Catholic Archiocese of Sydney which funded research demonstrating the capabilities of adult stem cells, and the U.S. Conference of Catholic Bishops working to pass federal legislation creating a nationwide public bank for umbilical cord blood stem cells.[70]

The Southern Baptist Convention opposes human embryonic stem cell research on the grounds that the "Bible teaches that human beings are made in the image and likeness of God (Gen. 1:27; 9:6) and protectable human life begins at fertilization."[71] However, it supports adult stem cell research as it does "not require the destruction of embryos."[71]

The United Methodist Church opposes human embryonic stem cell research, saying, "a human embryo, even at its earliest stages, commands our reverence."[72] However, it supports adult stem cell research, stating that there are "few moral questions" raised by this issue.[72]

The Assemblies of God opposes human embryonic stem cell research, saying, it "perpetuates the evil of abortion and should be prohibited."[73]

Islamic scholars generally favor the stance that scientific research and development of stem cells is allowed as long as it benefits society while causing the least amount of harm to the subjects. "Stem cell research is one of the most controversial topics of our time period and has raised many religious and ethical questions regarding the research being done. With there being no true guidelines set forth in the Qur'an against the study of biomedical testing, Muslims have adopted any new studies as long as the studies do not contradict another teaching in the Qur'an. One of the teachings of the Qur'an states that 'Whosoever saves the life of one, it shall be if he saves the life of humankind' (5:32), it is this teaching that makes stem cell research acceptable in the Muslim faith because of its promise of potential medical breakthrough."[74] This statement does not, however, make a distinction between adult, embryonic, or stem-cells. In specific instances, different sources have issued fatwas, or nonbinding but authoritative legal opinions according to Islamic faith, ruling on conduct in stem cell research. The Fatwa of the Islamic Jurisprudence Council of the Islamic World League (December 2003) addressed permissible stem cell sources, as did the Fatwa Khomenei (2002) in Iran. Several different governments in predominantly Muslim countries have also supported stem cell research, notably Saudi Arabia and Iran.

The First Presidency of The Church of Jesus Christ of Latter-day Saints "has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.[75]

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October 13th, 2022

Stem Cells Australia | Australian research, stem cell treatments and …

By daniellenierenberg

How are new treatments developed?

If you have seen a stem cell treatment advertised, featured in the media, or mentioned to you by a friend or fellow patient, it can be hard to work out if it may be an option for you.

Although there is a lot of attention surrounding the potential of stem cells, in reality, the range of diseases for which there are current proven stem cell treatments is quite small. Within Australia the only proven treatments available involving stem cells are corneal and skin grafting, and blood stem cell transplants for the treatment of some blood disorders, inherited immune and metabolic disorders, cancer and autoimmune diseases. There are many other potential treatments, but these are still in the research phase or in clinical trials and are yet to be proven as safe and effective.

This page provides a breakdown of the steps that should occur before a stem cell treatment makes it to you in a clinic, and identifies who should be looking after your interests.

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Stem Cells Australia | Australian research, stem cell treatments and ...

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October 13th, 2022

The eye and stem cells: the path to treating blindness

By daniellenierenberg

Replacing retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells have a number of important jobs, including looking after the adjacent retina. If these cells stop working properly due to damage or disease, then certain parts of the retina die. As the retina is the component of the eye responsible for detecting light, this leads to the onset of blindness. RPE cells can be damaged in a variety of diseases such as: age-related macular degeneration (AMD), retinitis pigmentosa and Lebers congenital aneurosis.

One way to treat these diseases would be to replace the damaged RPE cells with transplanted healthy cells. Unfortunately, it is not possible to take healthy RPE cells from donors so it is necessary to find another source of cells for transplantation. Scientists have recently produced new RPE cells from both embryonic stem cells and iPS cells in the lab. The safety of embryonic stem cell-derived RPE cells has been tested in phase I/II clinical trials for patients with Stargardts macular dystrophy, and for thse affected by AMD by a stem cell biotech company called Advanced Cell Technologies. Theresults of the trial, published in 2014, demonstrated safety and showed engraftment of the transplanted RPE cells. However, some participants experienced adverse side effects from the immunosuppression and the transplantation procedure itself. Interestingly, despite not being an endpoint of this trial, several patients also reported an improvement in vision.

A second Phase I/II trial exploringthe use of RPEs derived from human embryonic stem cells for people with wet AMDis currently underway in the United Kingdom. The first patient received their transplant in September 2015. This work, led by Prof Pete Coffey, is ongoing and is being carried out at Moorfields Eye Hospital as part of the London Project to Cure Blindness.

Finally, Japanese researcher, Dr Masayo Takahashi is leading a clinical trial in Japan which transplants RPE cells made from iPS cells into patients with wet AMD. The trial was put on hold for several months due to regulatory changes in Japan and concerns about mutations in an iPS cell product to be used in the trial. The trial has recommenced June 2016 and many await the results.

There areseveral other phase I or I/II clinical trials using pluripotent stem cells world-wideinvolving small numbers of participants. These trials are examining primarily the safety, but in some cases also the effectiveness, of the use of RPEs developed from pluripotent stem cells in dry and wet AMD and Stargardts macular degeneration.

Replacement of damaged RPE cells will only be effective in patients who still have at least part of a working retina, and therefore some level of vision (i.e. at early stages of the disease). This is because the RPE cells are not themselves responsible for seeing, but are actually responsible for supporting the seeing retina. Sight is lost in these types of diseases when the retina begins to degenerate because the RPE cells are not doing their job properly. So the RPE cells need to be replaced in time for them to support a retina that is still working. It is hoped that transplantation of new RPE cells will then permanently halt further loss of vision, and in some cases may even improve vision to some degree.

Replacing retinal pigment epithelial cells:Techniques for growing cells for therapies are being researched and tested in early clinical safety trials.

Replacing retinal cells

In many of the cases where vision is lost, we often find that the problem lies with malfunctioning retinal circuitry. Different disorders occur when particular, specialized cells in the circuit either stop working properly or die off. Despite the retina being more complicated than other components of the eye, it is hoped that if a source of new retinal cells can be found, we may be able to replace the damaged or dying cells to repair the retina. In addition, this approach may also help to repair damage caused to the optic nerve.

Again, scientists have turned to stem cell technology to provide the source of replacement cells. Several studies have now reported that both embryonic stem cells and iPS cells can be turned into different types of retinal cells in the lab. Within the eye, a type of cell called the Mller cell, which is found in the retina, is known to act as a stem cell in some species, such as the zebra fish. It has been suggested that this cell may also be able to act as a stem cell in humans, in which case it may provide another source of retinal cells for repair of the retina.

Unlike RPE cell transplantation, direct repair of the retina may allow patients who have already lost their vision to have it restored to some degree. This gives hope for patients with disorders like late-stage age-related macular degeneration, where the light-sensitive photoreceptor cells in the retina have already been lost. This type of research may also provide new treatments for people who suffer from retinal diseases like retinitis pigmentosa and glaucoma. However, despite encouraging evidence, such research is very much in its infancy. There are currently no patient clinical trials planned using this type of approach, as significant further research is still required first.

Replacing the nerve cells of the retina:Current research aims to understand how to produce retinal nerve cells that could be used in future therapies.

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October 13th, 2022

World’s first stem cell treatment for spina bifida delivered during fetal surgery – UC Davis Health

By daniellenierenberg

(SACRAMENTO)

Three babies have been born after receiving the worlds first spina bifida treatment combining surgery with stem cells. This was made possible by a landmark clinical trial at UC Davis Health.

The one-of-a-kind treatment, delivered while a fetus is still developing in the mothers womb, could improve outcomes for children with this birth defect.

Launched in the spring of 2021, the clinical trial is known formally as the CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele. Thirty-five patients will be treated in total.

The three babies from the trial that have been born so far will be monitored by the research team until 30 months of age to fully assess the procedures safety and effectiveness.

The first phase of the trial is funded by a $9 million state grant from the states stem cell agency, the California Institute for Regenerative Medicine (CIRM).

This clinical trial could enhance the quality of life for so many patients to come, said Emily, the first clinical trial participant who traveled from Austin, Tex. to participate. Her daughter Robbie was born last October. We didnt know about spina bifida until the diagnosis. We are so thankful that we got to be a part of this. We are giving our daughter the very best chance at a bright future.

Spina bifida, also known as myelomeningocele, occurs when spinal tissue fails to fuse properly during the early stages of pregnancy. The birth defect can lead to a range of lifelong cognitive, mobility, urinary and bowel disabilities. It affects 1,500 to 2,000 children in the U.S. every year. It is often diagnosed through ultrasound.

While surgery performed after birth can help reduce some of the effects, surgery before birth can prevent or lessen the severity of the fetuss spinal damage, which worsens over the course of pregnancy.

Ive been working toward this day for almost 25 years now, said Diana Farmer, the worlds first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.

As a leader of the Management of Myelomeningocele Study (MOMS) clinical trial in the early 2000s, Farmer had previously helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.

Farmer recruited bioengineer Aijun Wang specifically to help take that work to the next level. Together, they launched theUC Davis Health Surgical Bioengineering Laboratoryto find ways to use stem cells and bioengineering to advance surgical effectiveness and improve outcomes. Farmer also launched the UC Davis Fetal Care and Treatment Centerwith fetal surgeon Shinjiro Hirose and the UC DavisChildrens Surgery Center several years ago.

Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida.

Its believed that the stem cells work to repair and restore damaged spinal tissue, beyond what surgery can accomplish alone.

Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a patch, helped lambs with spina bifida walk without noticeable disability.

When the baby sheep who received stem cells were born, they were able to stand at birth and they were able to run around almost normally. It was amazing, Wang said.

When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

A pair of English bulldogs named Darla and Spanky were the worlds first dogs to be successfully treated with surgery and stem cells. Spina bifida, a common birth defect in this breed, frequently leaves them with little function in their hindquarters.

By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.

When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial.

For Emily, it was a lifeline that they couldnt refuse.

Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.

After screenings, MRI scans and interviews, Emily received the life-changing news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.

Farmer and Wangs team manufactures clinical grade stem cells mesenchymal stem cells from placental tissue in the UC Davis Healths CIRM-funded Institute for Regenerative Cures. The cells are known to be among the most promising type of cells in regenerative medicine.

The lab is aGood Manufacturing Practice(GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emilys fetal surgery.

Its a four-day process to make the stem cell patch, said Priya Kumar, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room. The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical.

During Emilys historic procedure, a 40-person operating and cell preparation team did the careful dance that they had been long preparing for.

After Emily was placed under general anesthetic, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect. The surgeons used a microscope to carefully begin the repair.

Then the moment of truth: The stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate.

The placement of the stem cell patch went off without a hitch. Mother and fetus did great! Farmer said.

The team declared the first-of-its-kind surgery a success.

On Sept. 20, 2021, at 35 weeks and five days gestation, Robbie was born at 5 pounds, 10 ounces, 19 inches long via C-section.

One of my first fears was that I wouldnt be able to see her, but they brought her over to me. I got to see her toes wiggle for the first time. It was so reassuring and a little bit out of this world, Emily said.

For Farmer, this day is what she had long hoped for, and it came with surprises. If Robbie had remained untreated, she was expected to be born with leg paralysis.

It was very clear the minute she was born that she was kicking her legs and I remember very clearly saying, Oh my God, I think shes wiggling her toes! said Farmer, who noted that the observation was not an official confirmation, but it was promising. It was amazing. We kept saying, Am I seeing that? Is that real?

Both mom and baby are at home and in good health. Robbie just celebrated her first birthday.

The CuRe team is cautious about drawing conclusions and says a lot is still to be learned during this safety phase of the trial. The team will continue to monitor Robbie and the other babies in the trial until they are 6 years old, with a key checkup happening at 30 months to see if they are walking and potty training.

This experience has been larger than life and has exceeded every expectation. I hope this trial will enhance the quality of life for so many patients to come, Emily said. We are honored to be part of history in the making.

Fighting One Disease or Condition per Day – Daily Kos

By daniellenierenberg

When I was young,,,

36 reasons to VOTE YES! For Your Scientist Friends

By Don C. Reed

Author, STEM CELL BATTLES, other books

http://www.stemcellbattles.com

Dear Friend of Regenerative Medicine:

For the next month, I will make available a daily summary of one aspect of stem cell researchmy laymans understanding of itdone by scientists connected to the California Institute for Regenerative Medicine (CIRM). Todays is spina bifida, tomorrow is stroke.

Mistakes are mine.

In most cases I have left out the scientists names. A few I have written about in my books, and those I felt free to credit.

All I ask is that when you step into the voting booth, please consider which political party is likely to fund such research, and vote accordingly.

Spina Bifida: total awards (3) Award value: $16,798,263

The condition is devastating, and lasts a lifetime. The baby has a part of its spine bulging out of its lower back. Accompanying symptoms are many, including: headaches, vomiting, weakness in the legs, bladder and bowel problems.

Current standard of care (in utero surgery) leaves 58% of patients unable to walk independently.

39% of affected population are Hispanic or Latino descent.

The condition may cost several million dollars per patient, over his or her lifetime.

Spina Bifida (SB) appears to be caused by a combination of genetic and environmental conditions, but no one is sure. How will CIRM fight such a thing?

One way is Placenta-derived mesenchymal stem cells, seeded on a Cook Biodesign extracellular Matrix. Think of a mesh screen, over the wound.

THERAPEUTIC MECHANISM: Mesenchymal stem cellssecrete growth factors (and) cytokinesprotecting motor neurons from cell deathtreatment increases the density of motor neurons in the spinal cord, leading to improved motor functionultimately reducing lower limb paralysis. (1)

Grant recipient Diana Farmer began science as a marine biologist, who doing research at the famous Woods Hole Institute. On the way to receive an award, she suffered a car accident, and changed her mind, working on human biology. She was the first woman to perform surgery on a baby in its mothers womb. (1)

She and Aijun Wang received a CIRM grant to co-launch the worlds first human clinical trial using stem cells to treat spina bifida.. (2)

1. https://en.wikipedia.org/wiki/Diana_L._Farmer

2. https://health.ucdavis.edu/health-news/newsroom/state-stem-cell-agency-funds-clinical-trial-for-spina-bifida-treatment/2020/11

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October 13th, 2022

UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology – Yahoo Finance

By daniellenierenberg

Both companies will collaborate to improve NurExone's drug development stages, from R&D to Quality Assurance

Company to host an investor webinar on Thursday, October 20th, 2022 at 11:00 AM EST

Calgary, Alberta and Oxford, United Kingdom--(Newsfile Corp. - October 12, 2022) - NurExone Biologic Inc. (TSXV: NRX) (FSE: J90) (the "Company" or "NurExone"), a biopharmaceutical company developing biologically-guided exosome therapy for patients with traumatic spinal cord injuries, is pleased to announce that the Company's wholly-owned subsidiary, NurExone Biologic Ltd., signed a non-binding Letter of Intent for a collaboration (the "Collaboration") with Nanometrix Ltd. ("Nanometrix"), a U.K.-based nanoparticle analysis company providing services to profile molecules of exosomes and their cargo.

Under the Collaboration, NurExone's exosomes and cargo samples will be processed and analyzed by Nanometrix, which will use its proprietary Artificial Intelligence (AI) software to extract and analyze morphological and population data to achieve detailed molecular profiling of the exosomes and quantify the siRNA cargo copy number per extracellular vesicle (EV), information which was far out of reach.

"Detailed molecular profiling of our exosomes and their siRNA cargo will facilitate a quality assurance program for repeatable, mass-production of ExoTherapies towards commercialization," said Dr. Lior Shaltiel, CEO of NurExone. "Nanometrix has the expertise and resources to perform this analysis in a highly professional manner and we look forward to working with them."

"The signing of this letter of intent is a first step towards a great milestone for Nanometrix," said Alexandre Kitching, CEO and Cofounder of Nanometrix. "We are thrilled to start this collaboration with NurExone as we believe in the future of exosomes as an advanced platform for drug delivery. We look forward to deploying our technology and assisting NurExone in gaining in-depth information about their siRNA-loaded exosomes and subsequently, improving the different stages of their drug development process."

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Exosomes are best defined as EVs that have emerged as promising guided nanocarriers for drug delivery and targeted therapy, and as alternatives to stem cell therapy. EVs are endosome-derived small membrane vesicles, approximately 30 to 150 nanometres in diameter, and are released into extracellular fluids by cells in all living systems. They are well-suited for small functional molecule delivery, and increasing evidence indicates that they have a pivotal role in cell-to-cell communication.

NurExone's ExoTherapy uses proprietary exosomes as biologically-guided nanocarriers to deliver specialized therapeutic compounds to targeted areas. The delivered molecules promote an environment that induces a healing process at the target location. For its first clinical indication of providing recovery of function to traumatic spinal cord injury (SCI) patients, NurExone used modified siRNA sequences as the delivered therapeutic molecules.

ExoTherapy is being developed as a revolutionary "off-the-shelf" intranasal product to treat traumatic spinal cord and brain injuries as well as other Central Nervous System indications. In preclinical studies of rats with a fully transected spinal cords, intranasal administration of ExoPTEN led to significant motor improvement, sensory recovery, and faster urinary reflex restoration.

Investor Webinar

The Company will be hosting a webinar to discuss its recent business highlights and growth outlook on Thursday, October 20th, 2022 at 11:00 AM EST.

Please click the link below to register for the webinar.https://us02web.zoom.us/webinar/register/WN_hqlWt1EUTrCy_ol_iJ2DmA

About Nanometrix

Nanometrix is a nanoparticle analysis start-up based in Oxford, UK that has developed unique end-to-end services to routinely create molecular profiles of nanoparticles from samples. Each profile delivers information currently out of reach such as the morphology, population dynamics and cargo copy number per nanoparticle. Nanometrix's software and services are currently deployed across labs and teams globally working on the development of novel therapeutics and diagnostics.

For additional information, please visit http://www.nanometrix.bio or contact us at info@nanometrix.bio

About NurExone Biologic Inc.

NurExone Biologic Inc. is a TSXV listed pharmaceutical company that is developing a platform for biologically-guided ExoTherapy to be delivered, non-invasively, to patients who suffered traumatic spinal cord injuries. ExoTherapy was conceptually demonstrated in animal studies at the Technion, Israel Institute of Technology. NurExone is translating the treatment to humans, and the company holds an exclusive worldwide license from the Technion for the development and commercialization of the technology.

For additional information, please visit http://www.nurexone.com or follow NurExone on LinkedIn, Twitter, Facebook, or YouTube.

For more information, please contact:

Inbar Paz-BenayounHead of CommunicationsPhone: +972-52-3966695Email: info@nurexone.com

For investors:Investor RelationsIR@nurexone.com+1 905-347-5569

FORWARD-LOOKING STATEMENTS

This press release contains certain forward-looking statements, including statements about the Company's future plans, the Letter of Intent, the development activities to be carried out pursuant to the Collaboration, the potential entering into of a commercial agreement between the parties and future potential manufacturing and marketing activities. Wherever possible, words such as "may", "will", "should", "could", "expect", "plan", "intend", "anticipate", "believe", "estimate", "predict" or "potential" or the negative or other variations of these words, or similar words or phrases, have been used to identify these forward-looking statements. These statements reflect management's current beliefs and are based on information currently available to management as at the date hereof. Forward-looking statements involve significant risk, uncertainties and assumptions. Many factors could cause actual results, performance or achievements to differ materially from the results discussed or implied in the forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the Company's early stage of development, lack of revenues to date, government regulation, market acceptance for its products, rapid technological change, dependence on key personnel, protection of the Company's intellectual property and dependence on the Company's strategic partners. These factors should be considered carefully and readers should not place undue reliance on the forward-looking statements. Although the forward-looking statements contained in this press release are based upon what management believes to be reasonable assumptions, the Company cannot assure readers that actual results will be consistent with these forward-looking statements. These forward-looking statements are made as of the date of this press release, and the Company assumes no obligation to update or revise them to reflect new events or circumstances, except as required by law.

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

NurExone is providing an updated release to the previously disseminated release from earlier today to remove a paragraph that was included in error.

To view the source version of this press release, please visit https://www.newsfilecorp.com/release/140289

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UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology - Yahoo Finance

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October 13th, 2022

Global Cell Therapy Market Report (2022 to 2028) – Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -…

By daniellenierenberg

DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market, By Use Type, By Therapy Type, By Product, By Technology & By Region- Forecast and Analysis 2022-2028" report has been added to ResearchAndMarkets.com's offering.

The Global Cell Therapy Market was valued at USD 14.86 Billion in 2021, and it is expected to reach a value of USD 35.95 Billion by 2028, at a CAGR of 13.45% over the forecast period (2022 - 2028).

Companies Mentioned

The cell therapy industry is being propelled forward by an increase in the number of clinical trials for cell-based treatments. As a result, global investment in research and clinical translation has increased significantly. The increasing number of ongoing clinical studies can be attributed to the presence of government and commercial funding bodies that are constantly providing funds to assist projects at various stages of clinical trials.

Top-down and bottom-up approaches were used to estimate and validate the size of the Global Cell Therapy Market and to estimate the size of various other dependent submarkets. The research methodology used to estimate the market size includes the following details: The key players in the market were identified through secondary research and their market shares in the respective regions were determined through primary and secondary research.

This entire procedure includes the study of the annual and financial reports of the top market players and extensive interviews for key insights from industry leaders such as CEOs, VPs, directors, and marketing executives.

All percentage shares split, and breakdowns were determined by using secondary sources and verified through Primary sources. All possible parameters that affect the markets covered in this research study have been accounted for, viewed in extensive detail, verified through primary research, and analyzed to get the final quantitative and qualitative data.

Segments covered in this report

The global cell therapy market is segmented based on Use-type, Therapy Type, Product, Technology, Application, and Region. Based on Use-type it is categorized into Clinical-use, and Research-use. Based on Therapy Type it is categorized into Allogenic Therapies, Autologous Therapies.

Based on Product it is categorized into Consumables, Equipment, Systems, and Software. Based on Technology it is categorized into Viral Vector Technology, Genome Editing Technology, Somatic Cell Technology, Cell Immortalization Technology, Cell Plasticity Technology, and Three-Dimensional Technology. Based on the region it is categorized into North America, Europe, Asia-Pacific, South America, and MEA.

Drivers

The increased demand for novel, better medicines for diseases such as cancer and CVD has resulted in an increase in general research efforts as well as funding for cell-based research. In November 2019, the Australian government released The Stem Cell Therapies Mission, a 10-year strategy for stem cell research in Australia.

The project would receive a USD 102 million (AU$150 million) grant from the Medical Research Future Fund (MRFF) to encourage stem cell research in order to develop novel medicines. Similarly, the UK's innovation agency, Innovate the UK, awarded USD 269,670 (GBP 267,000) in funding in September 2019 to Atelerix's gel stabilization technologies, with the first goal of extending the shelf-life of Rexgenero's cell-based therapies for storage and transport at room temperature.

Restraints

Despite technological advancements and product development over the last decade, the industry has been hampered by a lack of skilled personnel to operate complex devices like flow cytometers and multi-mode readers. Flow cytometers and spectrophotometers, which are both technologically advanced and extremely complex, generate a wide range of data outputs that require skill to analyze and review.

There is a global demand-supply mismatch for competent individuals, according to the National Accrediting Agency for Clinical Laboratory Sciences (NAACLS). Over the next decade, the UK and Europe are expected to face a severe shortage of lab capabilities, with medical laboratories being particularly hard hit.

Market Trends

The expansion of the cell therapy market was aided by the growing frequency of chronic illnesses. Chronic illness is defined as a condition that lasts one year or more and requires medical treatment, affects everyday activities, or both, according to the US Centers for Disease Control and Prevention (CDC).

It includes heart disease, cancer, diabetes, and Parkinson's disease. Patients with spinal cord injuries, type 1 diabetes, Parkinson's disease (PD), heart disease, cancer, and osteoarthritis may benefit from stem cells.

For more information about this report visit https://www.researchandmarkets.com/r/aqmxta

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Global Cell Therapy Market Report (2022 to 2028) - Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -...

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October 13th, 2022

Horizon Therapeutics plc Announces New UPLIZNA (inebilizumab-cdon) Data in Neuromyelitis Optica Spectrum Disorder (NMOSD) to be presented at ECTRIMS…

By daniellenierenberg

DUBLIN--(BUSINESS WIRE)--Horizon Therapeutics plc (Nasdaq: HZNP) today announced that new UPLIZNA analyses will be presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2022, Oct. 26-28. UPLIZNA is the first and only anti-CD19 B-cell-depleting humanized monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive NMOSD.

Presentation Details:

In addition, Horizon will host a symposium Thursday, Oct. 27 from 8:45-9:45 a.m. CEST called Step into the new era of NMOSD, chaired by Hans-Peter Hartung, M.D., Ph.D. and featuring presentations from Jrme de Sze Ph.D., Brian Weinshenker, M.D., and Orhan Aktas, M.D. Topics will include NMOSD diagnosis and care, advantages of CD19 treatments and the clinical relevance of UPLIZNA in NMOSD.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.1,2 Approximately 80% of all patients with NMOSD test positive for anti-AQP4 antibodies.3 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.4

Anti-AQP4 autoantibodies are produced by plasmablasts and some plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.5 Depletion of these CD19+ B-cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8,9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10,11

About UPLIZNA

INDICATION

UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%) and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see the Full Prescribing Information at http://www.UPLIZNA.com.

About Horizon

Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit http://www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

References

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Horizon Therapeutics plc Announces New UPLIZNA (inebilizumab-cdon) Data in Neuromyelitis Optica Spectrum Disorder (NMOSD) to be presented at ECTRIMS...

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October 13th, 2022

Physiology, Spinal Cord – StatPearls – NCBI Bookshelf

By daniellenierenberg

Introduction

Within the spinal column lies the spinal cord, a vital aspect of the central nervous system (CNS). The three primary roles of the spinal cord are to send motor commands from the brain to the body, send sensory information from the body to the brain, and coordinate reflexes. The spinal cordis organized segmentally, with thirty-one pairs of spinal nerves emanating from it. A spinal cord injury disrupts this conduit between the body and brain and canlead to deficits in sensation, movement, and autonomic regulation, as well as death.

The spinal cord is composed of gray and white matter, appearing in a cross-section as H-shaped gray matter surrounded by white matter. The gray matter consists of the cell bodies of motor and sensory neurons, interneurons,and neuropils (neuroglia cells and mostly unmyelinated axons). In contrast, the white matter is composed of interconnecting fiber tracts, which are primarily myelinated sensory and motor axons. The supports of the gray matters H make up the right dorsal, right ventral, left dorsal, and left ventral horns. Running longitudinally through the center of the spinal cord is the central canal, which is continuous with the brains ventricles and filled with cerebrospinal fluid (CSF).

The white matteris organized into tracts. Ascending tracts carry information from the sensory receptors to higher levels of the CNS, while descending tracts carry information from theCNS to the periphery. The major tracts and their most defining features are as follows:[1]

Ascending Tracts

Dorsal column: contains the gracile fasciculus and cuneate fasciculus, which togetherform the dorsal funiculus. The dorsal column is responsible for pressure and vibration sensation, two-point discrimination, movement sense, and conscious proprioception. The dorsal column decussates at the superior portion of the medulla oblongata and forms the medial lemniscus.

Lateral spinothalamic: carries pain and temperature information. The lateral spinothalamic tract decussates at the anterior commissure, two segments above the entry to the spinal cord.

Descending Tracts

Lateral and anterior corticospinal: involved in conscious control of the skeletal muscle. The majority of lateral corticospinal tract fibers decussate at the inferior portion of the medulla oblongata, while anterior corticospinal descends ipsilaterally in the spinal cord and decussates at the segmental level. The lateral corticospinal tract, also called the pyramidal tract, innervates primarily contralateralmuscles of the limbs, while the anterior corticospinal tract innervates proximal muscles of the trunk.

Vestibulospinal: carries information from the inner ear to control head positioning and is involved in modifying muscle tone to maintain posture and balance. The vestibulospinal tract does not decussate.

Rubrospinal: involved in the movement of the flexor and extensor muscles.The rubrospinal tract originates from the red nuclei in the midbrain and decussates at the start of its pathway.

There is a laminar distribution of neurons in the gray matter, characterized by density and topography:

Lamina II is composed mainly of islet cells with rostrocaudal axes, which contain GABA and are thought to be inhibitory, and stalked cells with dorsoventral dendritic trees.

Lamina V and VI are composed of medium-sized multipolar neurons that can be fusiform or triangular. These neurons communicate with the reticular formation of the brainstem.

Lamina VII is composed of homogenous medium-sized multipolar neurons and contains, in individual segments, well-defined nuclei, including the intermediolateral nucleus (T1-L1), which has autonomic functions, and the dorsal nucleus of Clarke (T1-L2), which make up the dorsal spinocerebellar tract.

Lamina VIII consists of neurons with dorsoventrally polarized dendritic trees.

Lamina IX has the cell bodies of motor neurons, with dendrites extending dorsally into laminas as far as VI. Lamina IX also has Renshaw cells, inhibitory interneurons, placed at the medial border of motor nuclei.

Neurulation begins in the trilaminar embryo when part of the mesoderm differentiates into the notochord. The formation of the notochord signals the overlying ectoderm to form the neural plate, the first structure that will become the nervous system. The neural plate folds in on itself, creating the neural tube, initially open at both ends and ultimately closed. From the neural tube comes the primitive brain and spinal cord.[9]The development of the nervous system begins seventeen days after gestation, and in the fifth week, myotomes start to form, allowing the development of rudimentary reflex circuitries. Myelination of the motor tracts begins in the first few months of life and continues into adolescence.

An interesting note is that reciprocal excitation changes to inhibition between nine and twelve months of age. Before that age, supraspinal descending fibers activate interneurons, resulting in extension or flexion. During this period of development, glycine and GABA are excitatory.[10]

The spinal cord is the conduit between the brain and the rest of the body. It sends motor commands from the motor cortex to the muscles of the body and sensory information from the afferent fibers to the sensory cortex. Additionally, the spinal cord can act without signals from the brain in certain instances. The spinal cord independently coordinates reflexes using reflex arcs.Reflex arcs allow the body to respond to sensory information without waiting for input from the brain. The reflex arc starts with a signal from a sensory receptor, which is carried to the spinal cord via a sensory nerve fiber, synapsed on an interneuron, carried over to the motor neuron, which stimulates an effector muscle or organ.[11]The spinal cord also has central pattern generators, which are interneurons that form the neural circuits, which control rhythmic movements. Although the existence of central pattern generators in humans is controversial, the lumbar spinal cord produces rhythmic muscle activation without volitional motor control or step-specific sensory feedback, suggesting their role in human movement.[12]

Three connective tissue layers,termed meninges, conceal the spinal cord. Directly lining the spinal cord is the pia mater, which also thickens to form the denticulate ligament, anchoring the spinal cord in the middle of the vertebral canal. The next layer of meninges is the arachnoid mater.Between the pia mater and arachnoid mater is the subarachnoid space, which contains CSF. On top of the arachnoid mater is the last layer of meninges, the dura mater, then the epidural space separating the meninges from the vertebral column.[13]

The spinal cord extends from the medulla oblongata of the brain stem at the level of the foramen magnum. In an adult human, the spinal cord gives rise to thirty-one pairs of spinal nerves, each of which originates from the adjacent spinal cord segment:

Spinal nerves emerge from the spinal cord as rootlets, whichjoin together to form two nerve roots.The anterior nerve roots contain motor fibers extending from the anterior horn to peripheral target organs. The motor neurons are multipolar, with at least two dendrites, a single axon, and one or more collateral branches. They control skeletal muscles and the autonomic nervous system. The posterior nerve roots contain sensory fibers and dorsal root ganglia. They contain sensory fibers transmitting sensory information from the periphery towards the CNS. The sensory neurons located at the dorsal root ganglia are pseudounipolar. The anterior and posterior nerve roots converge into spinal nerves, which split into dorsal and ventral rami.A dermatome is a skin area innervated by a single spinal nerve root (or spinal cord segment).

There are five spinal plexuses, which include sensory and motor nerves from the anterior rami:

Cervical plexus (C1-C5): the deep branches innervate neck muscles, and the superficial branches innervate the skin on the neck, head, and chest. The cranial plexus also has an autonomic function, including controlling the diaphragm and interactions with the vagus nerve.

Brachial (C5-T1): controls movement and sensation of the upper extremity.

Lumbar (L1-L4): controls movement and sensation of the abdominal wall, thigh, and external genitals.

Sacral (L4, L5, S1-S4): controls movement and sensation of the foot, leg, and thigh.

Coccygeal (S4, S5, Co): innervates the skin around the tailbone.

In adults, the spinal cord tapers to an end, termed the conus medullaris, at the second lumbar vertebra level. Past the conus medullaris, a bundle of spinal roots extends termed the cauda equina. The cauda equina and the subarachnoid space continue until S2 and is the target location for a lumbar puncture (spinal tap).

Electrophysiological Testing

Evoked potentials (EPs) measure electrical signals going to the brain and can determine whether there is motor or somatosensory impairment. The signal is detected by electroencephalography (EEG) or electromyography (EMG). Evoked potentialsmay be used to assess spinal cord damage in the setting of spinal cord injury and tumors, and measure functional impairment and predict disease progression in multiple sclerosis.[15]Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs)are frequentlyused intra-operatively for monitoring and can be used post-operatively as surrogate endpoints to check muscle strength and sensory status.[16]

Nerve conduction studies determine whether there has been an injury to a spinal nerve root, peripheral nerve, neuromuscular junction, muscle, cranial nerve, or spinal nerve. They can also be used to pinpoint spinal cord lesions.Nerve conduction studies work by stimulating nerves close to the skin or using a needle placed near a nerve or nerve root. Neurologists often use them with needle electromyograms.[17]

Lumbar Puncture

A lumbar puncture, or spinal tap, samples the CSF from the subarachnoid space. The needle to obtain the sample should be inserted between lumbar spinal canal levels L3 and L4 to avoid contact with the spinal cord.[18]TheCSF is then sent to a laboratory to establish whether any insult can be determined.For instance, a lumbar puncture can confirm or exclude bacterial meningitis, which will produce a cloudy fluid suggestive of a high leukocyte count. It is also important to know when not to use a lumbar puncture. Contraindications to lumbar puncture include signs of cerebral herniation, focal neurological signs, uncorrected coagulopathies, or cardiorespiratory compromise.[19]

Deep Tendon Testing

One aspect of theneurological exam is a test of the deep tendon reflexes, which are involuntary motor responses to various stimuli that function via reflex arcs within the spinal cord. They can be used to test the function of the motor and sensory nerves at specific spinal cord levels.Reflex grading is on a scale of 0 (absent reflex) to 5+ (sustained clonus).[20]Some commonly tested reflexes are as follows:

Additionally, the Babinski reflex, or the extensor plantar reflex, can be seen in newborns but is an abnormal response aftersix to twelve months of age. If the Babinski reflex is seen after 12 months of age, it may indicate an abnormality in the corticospinal system.[21]

Spinal Cord Injury

Primary spinal cord injury occurs due to local deformation of the spine, such as direct compression. Secondary spinal cord injury occurs following primary damage and involves cascades of biochemical and cellular processes, including electrolyte disturbances, free radical damage, edema, ischemia, and inflammation.[22]Secondary spinal cord injury has several phases: acute, subacute, and chronic. During the acute phase (up to 48 hours after the primary injury), hemorrhage and ischemia lead to ion balance disruption, excitotoxicity, and inflammation. During the subacute phase (up to two weeks following primary injury), there is a phagocytic response and a reactive proliferation of astrocytes, which leads to a glial scar in the chronic phase. The thinking is that scarification is the critical component to permanent disability because it prevents axonal regeneration; axons otherwise could regenerate, but their growth is blocked. However, that notion has been subject to challenge, and there are suggestions that astrocyte scar formation could aid in regeneration.[23]In the chronic phase (over six months after the primary injury), the scarification process is complete.[24]

Developmental

Open neural tube defects occur when there is a failure of the neural tube to close. If it fails to close at the cranial end, the fetusmay develop anencephaly. If the failure is at the caudal end, the fetusmay have myelomeningocele or open spina bifida. Craniorachischisis can also occur if the entire neural tube remains open. Closed neural tube defects are spinal cord development problems that are skin-covered, such as occult spina bifida.Folic acid supplements lower the risk of neural tube defects, although severe folate deficiency in mouse models does not lead to neural tube defects unless there is already a genetic predisposition. Suggestions are that folate can overcome a genetic predispositionfor adverse effects, potentially leading to neural tube defects.[25]

A spinal cord injury can be classified as complete or incomplete. A complete injury, based on the International Standard Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, developed by the American Spinal Cord Injury Association (ASIA), implies that there is no sensation at the inferior segments of the spinal cord (S4-S5); no deep anal pressure (DAP) or voluntary anal contraction (VAC) is present. If no perianal sensation is present and DAP and VAC are absent, the present function below the level of injury is a zone of partial preservation.[26]

An injury in the cervical region often results in quadriplegia if both sides of the spinal cord are affected and hemiplegia if only one side is affected. Nerves from C3, C4, and C5 stimulate the phrenic nerve, which controls the diaphragm, so injury to C4 and above may result in a permanent need for a ventilator. An injury to the thoracic region often limits the function of nerves related to the lower torso and lower extremities. Usually, it does not affect the upper torso and upper extremities, except in rare cases such as subacute posttraumatic ascending myelopathy (SPAM).[27]Injury to thespinal cord often causes loss of bowel and bladder control, loss of sexual function, and blood pressure dysregulation, as the spinal cordrelays autonomic and somatic information.

Syndromes

Several syndromes correlate with spinal cord injury. Central cord syndrome usually occurs in individuals who suffer a hyperextension injury, and it often leads to incomplete injury with weakness predominantly affecting the upper limbs. The reason for this phenomenon is the organization of the fibers in the spinal cord: the fibers running to the lower extremities are longer than those running to the upper extremities; the longer fibers are located more laterally in the spinal cord (L-L rule). As the central portion of the spinal cord is injured, there is a sparing of the fibers running to the lower extremities. Brown-Sequard syndrome is due to a spinal cord hemisection,leading to a complete loss of sensation at the level of the lesion, as well as deficits below the lesion loss of proprioception, vibration, and motor control, ipsilaterally, and a loss of pain and temperature sensation, contralaterally. Anterior cord syndrome is due to a compromised blood supply to the anterior two-thirds of the spinal cord, damaging the corticospinal and spinothalamic tracts.This syndrome is associated with several deficits at and below the lesion, including motor loss and a loss of pain and temperature sensation. However, light touch and joint position sense from the dorsal columns are left intact.[26]Injury to T12-L2 segmentsmay result in conus medullaris syndrome, while injury to L3-L5 segmentscan lead to cauda equina syndrome. Usually, these syndromes present as incomplete injuries and result in neurogenic bladder and/or bowel, loss of sexual function, and perianal loss of sensation.[28]

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October 5th, 2022

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Much-anticipated human trial aiming to repair spinal cord damage about to begin – ABC News

By daniellenierenberg

The Science Of Health: Are Spinal Cord Injuries Irreversible? Know Science Advances That Can Cure Them In The Future – ABP Live

By daniellenierenberg

Evaluating the Growth Prospects of the Global Nerve Repair & Regeneration Market at a CAGR of 6.5% | Emergen – EIN News

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Regenerative Therapies Market is Set to Grow at a CAGR of 8.7% by 2033, Propelled by Advancements in – EIN News

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Kadimastem Submits IND Application to the FDA for its Phase IIa Clinical Trial with AstroRx for the Treatment of ALS – Marketscreener.com

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My Back Is All F*cked Up 55-Year-Old Joe Rogan Curses at Worst Jiu-Jitsu for Painful Health Condition – EssentiallySports

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Brain and Spinal Cord Tumors: Hope Through Research

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14.3 The Brain and Spinal Cord Anatomy & Physiology

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Stem Cell Therapy for Spinal Cord Injury – PubMed

By daniellenierenberg

Spinal cord injury – Diagnosis and treatment – Mayo Clinic

By daniellenierenberg

Spinal Cord Injury: Hope Through Research | National Institute of …

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Stem cell controversy – Wikipedia

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Stem Cells Australia | Australian research, stem cell treatments and …

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The eye and stem cells: the path to treating blindness

By daniellenierenberg

World’s first stem cell treatment for spina bifida delivered during fetal surgery – UC Davis Health

By daniellenierenberg

Fighting One Disease or Condition per Day – Daily Kos

By daniellenierenberg

UPDATE: NurExone Signs Letter of Intent with Nanometrix for Its Exosome and Cargo Molecular Profiling AI-Driven Technology – Yahoo Finance

By daniellenierenberg

Global Cell Therapy Market Report (2022 to 2028) – Featuring Thermo Fisher Scientific, MaxCyte, Danaher and Avantor Among Others -…

By daniellenierenberg

Horizon Therapeutics plc Announces New UPLIZNA (inebilizumab-cdon) Data in Neuromyelitis Optica Spectrum Disorder (NMOSD) to be presented at ECTRIMS…

By daniellenierenberg

Physiology, Spinal Cord – StatPearls – NCBI Bookshelf

By daniellenierenberg

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