Back to Browse Journals Journal of Neurorestoratology Volume 5

Zhijian Cheng, Xijing He

Department of Orthopedics, The Second Affiliated Hospital of Xian Jiaotong University, Xian, Shaanxi, Peoples Republic of China

Abstract: Spinal cord injury (SCI) is a traumatic event that involves not just an acute physical injury but also inflammation-driven secondary injury. Macrophages play a very important role in secondary injury. The effects of macrophages on tissue damage and repair after SCI are related to macrophage polarization. Stem cell transplantation has been studied as a promising treatment for SCI. Recently, increasing evidence shows that stem cells, including mesenchymal stem, neural stem/progenitor, and embryonic stem cells, have an anti-inflammatory capacity and promote functional recovery after SCI by inducing macrophages M1/M2 phenotype transformation. In this review, we will discuss the role of stem cells on macrophage polarization and its role in stem cell-based therapies for SCI.

Keywords: stem cells, macrophages, spinal cord injury, polarization

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Science Daily

Your brain's got rhythm: Synthetic brain mimics Science Daily Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem ... and more »

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Your brain's got rhythm: Synthetic brain mimics - Science Daily

Spinal Cord Stem Cells Comments Off on Your brain’s got rhythm: Synthetic brain mimics – Science Daily | February 15th, 2017

February 14, 2017 Salk scientists create synthetic brain systems called 'circuitoids' to better understand dysfunctional movements in Parkinson's, ALS and other diseases. Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem cells and termed a 'circuitoid.' Credit: Salk Institute

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that depend on the rhythmic firing of neurons. Yet the neural circuitry underpinning such seemingly ordinary behaviors is not fully understood, even though better insights could lead to new therapies for disorders such as Parkinson's disease, ALS and autism.

Recently, neuroscientists at the Salk Institute used stem cells to generate diverse networks of self-contained spinal cord systems in a dish, dubbed circuitoids, to study this rhythmic pattern in neurons. The work, which appears online in the February 14, 2017, issue of eLife, reveals that some of the circuitoidswith no external promptingexhibited spontaneous, coordinated rhythmic activity of the kind known to drive repetitive movements.

"It's still very difficult to contemplate how large groups of neurons with literally billions if not trillions of connections take information and process it," says the work's senior author, Salk Professor Samuel Pfaff, who is also a Howard Hughes Medical Institute investigator and holds the Benjamin H. Lewis Chair. "But we think that developing this kind of simple circuitry in a dish will allow us to extract some of the principles of how real brain circuits operate. With that basic information maybe we can begin to understand how things go awry in disease."

Nerve cells in your brain and spinal cord connect to one another much like electronic circuits. And just as electronic circuits consist of many components, the nervous system contains a dizzying array of neurons, often resulting in networks with many hundreds of thousands of cells. To model these complex neural circuits, the Pfaff lab prompted embryonic stem cells from mice to grow into clusters of spinal cord neurons, which they named circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to see with the naked eye, and with different ratios of neuronal subtypes.

With molecular tools, the researchers tagged four key subtypes of both excitatory (promoting an electrical signal) and inhibitory (stopping an electrical signal) neurons vital to movement, called V1, V2a, V3 and motor neurons. Observing the cells in the circuitoids in real time using high-tech microscopy, the team discovered that circuitoids composed only of V2a or V3 excitatory neurons or excitatory motor neurons (which control muscles) spontaneously fired rhythmically, but that circuitoids comprising only inhibitory neurons did not. Interestingly, adding inhibitory neurons to V3 excitatory circuitoids sped up the firing rate, while adding them to motor circuitoids caused the neurons to form sub-networks, smaller independent circuits of neural activity within a circuitoid.

"These results suggest that varying the ratios of excitatory to inhibitory neurons within networks may be a way that real brains create complex but flexible circuits to govern rhythmic activity," says Pfaff. "Circuitoids can reveal the foundation for complex neural controls that lead to much more elaborate types of behaviors as we move through our world in a seamless kind of way."

Because these circuitoids contain neurons that are actively functioning as an interconnected network to produce patterned firing, Pfaff believes that they will more closely model a normal aspect of the brain than other kinds of cell culture systems. Aside from more accurately studying disease processes that affect circuitry, the new technique also suggests a mechanism by which dysfunctional brain activity could be treated by altering the ratios of cell types in circuits.

Explore further: Scientists discover new mechanism of how brain networks form

More information: Matthew J Sternfeld et al, Speed and segmentation control mechanisms characterized in rhythmically-active circuits created from spinal neurons produced from genetically-tagged embryonic stem cells, eLife (2017). DOI: 10.7554/eLife.21540

Journal reference: eLife

Provided by: Salk Institute

Scientists have discovered that networks of inhibitory brain cells or neurons develop through a mechanism opposite to the one followed by excitatory networks. Excitatory neurons sculpt and refine maps of the external world ...

A new study presented in the journal Nature could change the view of the role of motor neurons. Motor neurons, which extend from the spinal cord to muscles and other organs, have always been considered passive recipients ...

When you're taking a walk around the block, your body is mostly on autopilotyou don't have to consciously think about alternating which leg you step with or which muscles it takes to lift a foot and put it back down. That's ...

We humans walk with our feet. This is true, but not entirely. Walking, as part of locomotion, is a coordinated whole-body movement that involves both the arms and legs. Researchers at the Biozentrum of the University of Basel ...

Dr. Kevin Collins carefully places a petri dish with what looks like a blotch of yellowish slime under a microscope. Magnified, the slime comes alive as hundreds of translucent worms, known as Caenorhabditis elegans, slither ...

Imagine yourself sitting in a noisy caf trying to read. To focus on the book at hand, you need to ignore the surrounding chatter and clattering of cups, with your brain filtering out the irrelevant stimuli coming through ...

Not everyone is Fred Astaire or Michael Jackson, but even those of us who seem to have two left feet have got rhythmin our brains. From breathing to walking to chewing, our days are filled with repetitive actions that ...

Whether we're navigating a route to work or browsing produce at the grocery store, our brains are constantly making decisions about movement: Should I cross the street now or at the intersection? Should I reach for the red ...

Pain is a signal of actual or potential damage to the body, so it is natural to think of it as a localized sensation: knee pain in the knee, back pain in the back and so on.

Researchers from the University of Toronto, Canada, have discovered a reason why we often struggle to remember the smaller details of past experiences.

The feel-good brain chemical dopamine appears to play a role in the development of a healthy bond between a mother and baby, a new study suggests.

Proteins are the building blocks of all cells. They are made from messenger RNA (mRNA) molecules, which are copied from DNA in the nuclei of cells. All cells, including brain cells regulate the amount and kind of proteins ...

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Your brain's got rhythm - Medical Xpress

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Transparency Market Research, in a report titled Stem Cells Market Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018, states that the global stem cells market is projected to witness remarkable growth from 2012 to 2018, fueled by increasing government support, unmet medical needs, rising stem cell banking services, and growing medical tourism. Driven by these factors, the global stem cells market is anticipated to expand at a 24.20% CAGR during the forecast period, rising from a value of US$26.2 bn in 2013 to US$119.5 bn by 2018.

Browse the full Stem Cells Market (Adult, Human Embryonic , Induced Pluripotent, Rat-Neural, Umbilical Cord, Cell Production, Cell Acquisition, Expansion, Sub-Culture) Global Industry Analysis, Size, Share, Growth, Trends and Forecast, 2012 2018 report at http://www.transparencymarketresearch.com/stem-cells-market.html

Rise in disposable income in emerging economies, the increasing prevalence of neurodegenerative disorders, development of the contract research industry, and replacement of animal tissue in drug discovery are also anticipated to contribute towards the overall growth of the stem cells market.By product, the stem cells market is categorized into adult stem cells, induced pluripotent stem cells, very small embryonic-like stem cells, human embryonic stem cells, and rat neural stem cells. Adult stem cells, which dominated the overall market in 2011, include mesenchymal stem cells, dental stem cells, neuronal stem cells, hematopoietic stem cells, and umbilical cord stem cells.

On the basis of technology, the stem cells market is segmented into stem cell acquisition, production, cryopreservation, and expansion and sub-culture. Stem cell acquisition is the largest as well as the most rapidly developing technological segment and includes bone marrow harvesting, umbilical cord blood, and apheresis. The segment of stem cell production includes cloning, isolation, in-vitro fertilization, and cell culture.

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The leading companies profiled in the stem cells market report are Osiris Therapeutics, Advanced Cell Technology, Cellartis AB, Bioheart, Cellular Engineering Technologies, Biotime Inc., Cytori Therapeutics Inc., Angel Biotechnology, Stemcelltechnologies Inc., California Stem Cell Inc., Brainstorm Cell Therapeutics, and Celgene Corporation Inc. These players are analyzed based on aspects such as company and financial overview, product portfolio, business strategies, and recent developments.

Global Stem Cells Market, By Product

Adult Stem Cells Hematopoietic Stem Cells Mesenchymal Stem Cells Neuronal Stem Cells Dental Stem Cells Umbilical Cord Stem Cells Human Embryonic Stem Cells Induced Pluripotent Stem Cells Rat Neural Stem Cells Very Small Embryonic-Like Stem Cells Global Stem Cells Market, By Technology

Stem Cell Acquisition Bone Marrow Harvest for Stem Cells Apheresis for Stem Cells Umbilical Cord Blood Stem Cell Production Therapeutic Cloning for Stem Cells Stem Cells Production By In Vitro Fertilization Stem Cell Isolation Stem Cell Culture Stem Cell Cryopreservation Stem Cells Expansion and Sub-Culture Global Stem Cells Market, By Application

Regenerative Medicine Neurology Orthopedics Oncology Hematology Cardiovascular and Myocardial Infarction Injuries Diabetes Liver Disorders Incontinence Others Drug Discovery and Development Global Stem Cells Market, By Geography

North America Asia Pacific Europe Rest of the World

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Stem Cells Market Share, Size, Growth & Forecast 2018 Illuminated by New Report - Satellite PR News (press release)

Spinal Cord Stem Cells Comments Off on Stem Cells Market Share, Size, Growth & Forecast 2018 Illuminated by New Report – Satellite PR News (press release) | February 15th, 2017

After a spinal cord injury, many of the nerve fibers at the injury site lose their insulating layer of myelin. As a result, the fibers are no longer able to properly transmit signals between the brain and the spinal cord contributing to paralysis. Unfortunately, the spinal cord lacks the ability to restore these lost myelin-forming cells after trauma.

Tissue engineering in the spinal cord involves the implantation of scaffold material to guide cell placement and foster cell development. These scaffolds can also be used to deliver stem cells at the site of injury and maximize their regenerative potential.

When the spinal cord is damagedeither accidentally (car accidents, falls) or as the result of a disease (multiple sclerosis, infections, tumors, severe forms of spinal bifida, etc.)it can result in the loss of sensation and mobility and even in complete paralysis.

For publications on spinal cord injuries, please click here.

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Spinal Cord Injury and Stem Cell Therapy

Spinal Cord Stem Cells Comments Off on Spinal Cord Injury and Stem Cell Therapy | February 12th, 2017

Forbes

This Breakthrough In Biotech Has Enormous Investment Potential Forbes Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. That's when the company first released results about ...

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This Breakthrough In Biotech Has Enormous Investment Potential - Forbes

Spinal Cord Stem Cells Comments Off on This Breakthrough In Biotech Has Enormous Investment Potential – Forbes | February 11th, 2017

Greg Iger/Keck Medicine of USC

Kristopher Boesen, who broke his neck in a car accident, regained the ability to move his arms and hands after his spinal cord was injected with stem cells.

Two years after having a stroke at 31, Sonia Olea Coontz remained partially paralysed on her right side. She could barely move her arm, had slurred speech and needed a wheelchair to get around. In 2013, Coontz enrolled in a small clinical trial. The day after a doctor injected stem cells around the site of her stroke, she was able to lift her arm up over her head and speak clearly. Now she no longer uses a wheelchair and, at 36, is pregnant with her first child.

Coontz is one of stem-cell therapy's miracle patients, says Gary Steinberg, chair of neurosurgery at Stanford School of Medicine in California, and Coontz's doctor. Conventional wisdom said that her response was impossible: the neural circuits damaged by the stroke were dead. Most neuroscientists believed that the window for functional recovery extends to only six months after the injury.

Stem-cell therapies have shown great promise in the repair of brain and spinal injuries in animals. But animal models often behave differently from humans nervous-system injuries in rats, for example, heal more readily than they do in people. Clinical trial results have been mixed. Interesting signals from small trials have faded away in larger ones. There are plenty of unknowns: which stem cells are the right ones to use, what the cells are doing when they work and how soon after an injury they can be used.

The field is still young. Stem cells are poorly understood, and so is what happens after a spinal-cord injury or stroke. Yet, there are success stories, such as Coontz's, which seem to show that therapy using the right sort of stem cell can lead to functional improvements when tried in the right patients and at the right time following an injury. Researchers are fired up to determine whether stem-cell therapies can help people who are paralysed to regain some speech and motor control and if so, what exactly is going on.

Neurologists seeking functional restoration are up against the limited ability of the human central nervous system to heal. The biology of the brain and spinal cord seems to work against neuroregeneration, possibly because overgrowth of nerves could lead to faulty connections in the finely patterned architecture of the brain and spine, says Mark Tuszynski, a neurologist at the University of California, San Diego. Local chemical signals in the central nervous system tamp down growth. Over time, scarring develops, which prevents the injury from spreading, but also keeps cells from entering the site.

It's really hard to fix the biology, says Charles Yu Liu, a neurosurgeon and director of the University of Southern California Neurorestoration Center in Los Angeles. Stem cells seem to promise a workaround.

So far, neural regeneration cell therapy has had only anecdotal success, leaving investors and patients disappointed. In people with Parkinson's disease, for example, neurosurgeons replaced dead and dying dopamine-producing neurons with fetal neurons. Although initial results were promising, in larger studies, patients reported involuntary movements. Another effort tried treating people who'd had a stroke with cells derived from tumours; the results were mixed, and researchers were uneasy about the cells' cancerous source.

In recent years, researchers have had success with stem cells coaxed to develop into particular cell types, such as neural support cells. Tuszynski has showed how well stem cells can work at least, in animal models1. His group implanted neural stem cells derived from human fetal tissue into rats with severe spinal-cord injuries. Seven weeks later, the cells had bridged the gap where the spinal cord had been cut and the animals were able to walk again. The cells used in the study were manufactured by Neuralstem of Rockville, Maryland. The group has shown that other kinds of stem cell, including those derived from adult tissue, also work. Tuszynski has seen similar results in a rat spinal-cord-injury model, using neural stem cells made from the tissues of a healthy 86-year-old volunteer2.

Mark Tuszynski/Ken Kadoya/Ref. 3

Regeneration of axons (red) beyond implanted neural progenitor cells (green) in a rat with a spinal injury.

But animal studies are also making it clear that simply regrowing the connective wiring of the nervous system to bridge damaged areas is not enough, says Zhigang He, who studies neural repair at the Harvard Stem Cell Institute in Cambridge, Massachusetts. No matter what the animal model is, he says, the axons don't always grow into the right places. It's not enough to have a nerve, that nerve must become part of a functional circuit.

There is growing evidence that besides becoming replacement nerves, stem cells perform other functions they also seem to generate a supportive milieu that may encourage the natural recovery process or prevent further damage after an injury. Many types of neural stem cell secrete a mix of molecules that unlock suppressed growth pathways in nerves. Earlier this year, Tuszynski reported that any sort of spinal-cord stem cell, whether derived from adult tissues or embryos, from humans, rats or mice, could trigger native neural regeneration in rats3. But his success in rats has not yet translated into clinical trials. More work is needed, Tuszynski says, to determine which type of cell will work best for which particular injury.

For people who have had a stroke or spinal-cord injury, physical therapy is currently the best hope for recovery in the weeks and months after the injury. The brain is plastic and can co-opt other circuits and pathways to compensate for damage and to restore function. Once the inflammation ebbs and the brain adjusts, people can start to regain function. But the window of opportunity is short. Most people don't make functional gains after six months.

That timeline is why the remarkable recovery enjoyed by Coontz and other patients with chronic stroke in the same clinical trial is so surprising, says Steinberg. This changes our whole notion of recovery, he says. There were 18 people in the trial Coontz took part in, and all were treated using stem cells manufactured by SanBio of Mountain View, California. The company's cells are bone-marrow-derived mesenchymal stem cells. The cells are treated with a DNA fragment that is transiently expressed in them, and causes changes in their protein-expression patterns. In animal studies, these cells promote the migration and growth of native neural stem cells, among other effects.

The trial, which was designed to look at safety as well as efficacy, recruited patients after an ischaemic stroke. During this kind of stroke, a clot cuts off the blood supply to part of the brain, causing significant damage. Patients in the trial had all had ischaemic strokes deep in the brain 736 months earlier past the 6-month window for significant recovery. Each patient was injected with either 2.5 million, 5 million or 10 million of SanBio's cells4. Steinberg has followed participants for 24 months; an interim study at 12 months reported that most patients showed functional improvements. Some, like Coontz, achieved almost complete recovery.

What is not clear, however, is what the stem-cell injections do in the brain. In animal studies, the SanBio cells do not turn into neurons, but seem to send supporting signals to native cells in the brain. Indeed, preclinical research shows that the cells do not integrate into the brain most die after 12 months. Instead, the cells seem to secrete growth factors that encourage the formation of new neurons and blood vessels, and foster connections called synapses between neurons. And in rats, the nerve-cell connections that extended from one side of the brain to the other, as well as into the spinal cord, lasted, even though the injected cells did not4.

But these mechanisms are not sufficient to explain Coontz's overnight restoration of function, says Steinberg. He is entertaining several hypotheses, including that the needle used to deliver the cells may have had some effect. One week after treatment, we saw abnormalities in the premotor cortex that went away after one month, he says. The size of these microlesions was strongly correlated with recovery at 12 months. A similar effect can happen when electrodes are implanted in the brains of people with Parkinson's, although this deep-brain stimulation quietens tremors for only a short time. The people who'd had a stroke had a lasting recovery, suggesting that both the needle and the stem cells may have played a part.

The SanBio trial was small, and did not have a placebo control; the company is now recruiting for a larger phase II trial. Of the 156 participants that will be recruited, two-thirds will have cells injected the others will have a sham surgery. Even the trial surgeons, including Steinberg, will not know who is getting which treatment. The main outcome measure will be whether patients' motor-skill scores improve on a test called the Fugl-Meyer Motor scale six months after treatment. Participants will be monitored for at least 12 months, and will also be evaluated with tests that look for changes in gait and dexterity. Meanwhile, Steinberg plans to study microlesions in animal models of stroke to determine whether they do have a role in recovery.

An ongoing clinical trial evaluating escalating doses of neural stem cells in patients with acute spinal-cord injuries is also looking promising. Asterias Biotherapeutics of Fremont, California, coaxes the cells to develop into progenitors of oligodendrocytes, a type of support cell that's found in the brain and spinal cord and that creates a protective insulation for neuronal axons.

The trial tests the safety and efficacy of administering these cells to people with recent cervical, or neck-level, spinal-cord injury. Interim results for patients who had received the two lower doses were presented at the International Spinal Cord Society meeting in September. After 90 days, 4 patients who received 10 million cells showed improved motor function; a fifth patient had not reached the 90-day mark yet. At one year, the three patients receiving a lower dose of two million cells showed measurable improvement in motor skills.

These cells were initially developed by Geron, a biotechnology company that has since moved away from regenerative medicine. Before spinning out Asterias in 2013, Geron had run a safety trial of the cells in people with a chronic lower-back injury. No issues were identified, and the US Food and Drug Administration agreed to let the company test the cells in patients who'd been recently injured. Asterias focused the current trial on patients with cervical injuries because these are closer to the brain, so new nerve cells have a shorter distance to grow to gain functional improvements. People with severe cervical spine injuries are typically paralysed below the level of the damage. The company's hope is to restore arm and hand function for people with such injuries, potentially making a tremendous difference to a person's independence and quality of life.

Asterias seems to have realized this hope in at least one patient who received one of the higher doses. Kristopher Boesen, who is 21, has had a dramatic recovery. In March, Boesen's car fishtailed in a rainstorm; he hit a telephone pole and broke his neck. About a month later, Boesen was still paralysed below the injury, and his neurological improvements seemed to have plateaued. His doctors at a trauma centre in Bakersfield, California, were in touch with Liu, who is an investigator in the Asterias trial. As soon as he was stable, Boesen travelled to Los Angeles to join the trial.

Liu injected Boesen's spinal cord with Asterias's cells in April. Two days later, Boesen started to move his hands, and in the summer, he regained the ability to move the toes on one foot.

Asterias Biotherapeutics

A surgeon prepares to inject stem cells to treat a spinal injury as part of Asterias's clinical trial.

Liu is excited about Boesen's response. He was looking at being quadriplegic, and now he's able to write, lift some weights with his hands, and use his phone, says Liu. For somebody to improve like this is highly unusual I want to be jumping out of my shoes. But Liu cautions that this is still a small trial, and that Boesen's response is just one anecdotal report. Until the results are borne out in a large, placebo-controlled clinical trial, Liu will remain earthbound.

The trial is currently recruiting between 5 and 8 patients for another cohort that will receive a doubled dose of 20 million cells. As the trial goes on, Asterias hopes to find clues about the underlying mechanism. We're looking at changes in the anatomy of the injury, says the company's chief scientific officer, Jane Lebkowski. She says that there is some evidence that axons have traversed the injury site in patients who have recovered function. Preclinical work suggests that the cells might be sending growth-encouraging chemical signals to the native tissue. And, as support cells, the astrocytes may also be preventing more neurons from dying in the aftermath of the acute spinal injury.

Not all clinical trials have performed so well. The SanBio and Asterias results are positive signals in a sea of negative or mixed trials. For example, StemCells of Newark, California, terminated its phase II trial of stem cells for the treatment of spinal-cord injury in May, and shortly afterwards announced that it will restructure its business. The company declined to comment for this article.

Physicians such as Liu and Steinberg temper their public enthusiasm about stem-cell therapies, so as not to give false hope to desperate patients. People with paralysing injuries or those who have a neurodegenerative disease are easy marks for unscrupulous stem-cell clinics, whose therapies are not only unproven, but also come with risks.

Patients say, 'Go ahead, doc, you can't make me any worse,' says Keith Tansey, a neurologist and researcher at the Methodist Rehabilitation Center in Jackson, Mississippi, and president-elect of the American Spinal Injury Association. Unfortunately, that is not the case. Cell therapies given at a clinic, outside the context of a clinical trial, can lead to chronic pain, take away what little function a patient has left and render a patient ineligible for future studies, says Tansey. He has seen the consequences in his clinical practice. I treated a kid who had two different tumours in his spinal cord from two different individuals' cells, he says.

Many unanswered questions remain about whether stem cells can heal the central nervous system in people, and how they might do it. Researchers also don't know what cells are the best to use. Is it enough for them to grow into supportive cells that send friendly growth signals, or is it better that they grow into replacement neurons? The answer is likely to differ depending on the site and nature of the disease or injury. If the stem cells are producing supportive factors that encourage growth and repair, it might be possible, says He, to discern what these are and give them directly to patients. But biologists are not yet close to deciphering the recipe for such a cocktail.

Every time we get an experiment done we realize it's more complex than we thought it would be.

Tansey agrees that there are many unknowns and these seem to be multiplying. Every time we get an experiment done we realize it's more complex than we thought it would be, he says. Tansey thinks that the best way to resolve such uncertainties is with carefully regulated clinical trials. Rat models will only tell us so much the human nervous system is much larger and is wired differently. If stem cells help patients such as Coontz and Boesen to regain their speech and give them greater independence without adverse effects, then it makes sense to continue, he says, even without knowing all the details of how they work.

Until these positive, but small, results are replicated in larger, controlled clinical trials, neurologists are containing their optimism. I'd like to hear of any clinical trial that has more than an anecdotal benefit, says Tansey. And Liu is anticipating the day when he won't need to control his elation. In a few years, perhaps there will be a genuine opportunity to jump for joy.

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Neuroscience: New nerves for old - Nature.com

Spinal Cord Stem Cells Comments Off on Neuroscience: New nerves for old – Nature.com | February 8th, 2017

A New Delhi clinic that has claimed to help paralyzed Canadians walk again by injecting them with stem cells now says it can use the same treatment to make children with Down syndrome almost near normal.

Nutech Mediworld says it has treated up to 16 newborns, toddlers and older children with Down syndrome. According to its medical director, Geeta Shroff, we have seen that patients actually start improving clinically they become almost at par for their age.

Canadian experts say the bold claim risks raising false expectations and public confusion, much like the now-discredited Liberation therapy for multiple sclerosis, and that its playing off the over-hyped belief stem cells have the potential to cure almost anything.

Its also the latest controversy over stem cell tourism, and the growing number of clinics worldwide marketing pricey, unregulated and unproven treatments.

Nutech Mediworld charges US$5,000 to $6,000 per week for its stem cell-based therapies. The clinic says it has treated such incurable conditions as spinal cord injury and cerebral palsy. Around 20 Canadians have sought treatment at the clinic for paralyzing spinal cord injuries, spending upwards of $US48,000 each. Shroff says some of her patients have regained the ability to walk with walkers.

More recently, she began working with Down syndrome, one of the most common chromosomal disorders worldwide.

Most cases are caused by a random error in cell division. The child ends up with three copies of chromosome 21, instead of the usual two.

That extra copy causes abnormal neuronal development and changes in the central nervous system, Shroff says, leading to persistent developmental delays.

Human embryonic stem cells injected into a childs muscles and bloodstreamcan regenerate and repair that damaged brain, she says. They also work at the genetic level, she claims.

In a single case published last year, Shroff reported treating a two-month-old baby boy in September 2014 diagnosed with Down syndrome at birth. The infant had delayed milestones, lack of speech, subnormal understanding and subnormal motor skills, she wrote.

After two stem cell therapy sessions, the baby started babbling and crawling, she reported. He had improved muscle tone. He was social and was able to recognize near ones.

The child became almost as near normal as possible cognitively

The child became almost as near normal as possible cognitively, Shroff told the Post in an interview. Today, hes talking; hes walking. He was at par with normal children on analysis.

The former infertility specialist uses embryonic stem cells developed from a single fertilized egg donated by an IVF patient 17 years ago. According to Shroff, We have witnessed no adverse events at all.

The Down syndrome treatments, reported by New Scientist, have raised skepticism and alarm. Its not at all clear what cells shes actually putting in patients, says renowned developmental biologist Janet Rossant, senior scientist at the Hospital for Sick Children Research Institute in Toronto.

By just putting them into the bloodstream theres no way to imagine they could contribute to the right tissues.

Embryonic stem cells can also form teratomas benign tumours and masses composed of lung cells, tufts of hair, teeth, bone and other tissues.

The gold standard for any therapy would be a clinical trial comparing treated with untreated children and vetted through proper regulatory systems that clearly she is not going through, Rossant says.

The Ottawa Hospitals Dr. Duncan Stewart, who is leading the first trial in the world of a genetically enhanced stem cell therapy for heart attack, says theres a remote chance embryonic stem cells could help with Down syndrome. But its a stretch. The injected cells would also likely be rejected and die off with days, he believes. If the cells are disappearing within days, how are they working?

This is a very vulnerable population Theyre very vulnerable to people who are selling hope and have no basis for it

This is a very vulnerable population, Stewart adds. Theyre very vulnerable to people who are selling hope and have no basis for it.

But stem cells have taken on almost mystical appeal.

Theyve become a pop culture phenomenon, says healthy policy expert Timothy Caulfield, of the University of Alberta. The field itself is guilty of making breathless announcements about breakthroughs and cutting edge, he says. And people can market that kind of language.

This kind of nonsense doesnt help.

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From Down syndrome to 'near normal'? New Delhi clinic makes stem cell claims that worry experts - National Post

Spinal Cord Stem Cells Comments Off on From Down syndrome to ‘near normal’? New Delhi clinic makes stem cell claims that worry experts – National Post | February 7th, 2017

For many people suffering from disabling conditions, such as Parkinsons disease, spinal injury and paralysis, heart disease, and even cancer, announcements in the press around breakthroughs in stem cell research undoubtedly bring hope.

Keeping the balance between hope and hype is a difficult one, particularly when there are vulnerable and suffering people relying on the hope medical research offers. As Australian of the Year, Emeritus Professor Alan Mackay-Sim, stated in his acceptance speech, there are now many clinical trials being performed in Australia and around the globe, to determine whether the delivery of certain types of cells, including some grown from stem cells, into the spinal column can allow patients with spinal cord injury to regain function.

For these individuals, even a small gain of functionis a major advance. However, as yet there is no stem cell silver bullet.

And stem cells that have shown promise can also cause complications. It was also reported a paraplegic woman developed a growth in her spine many years after an unsuccessful spinal stem cell treatmentHence, more research to test these and other types of cells in well-run clinical trials is required to move from anecdote to safe and effective therapies.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:The future of stem cells: tackling hype versus hope

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Hype versus hope: Deciphering news about stem cell breakthroughs - Genetic Literacy Project

Spinal Cord Stem Cells Comments Off on Hype versus hope: Deciphering news about stem cell breakthroughs – Genetic Literacy Project | February 7th, 2017

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The word "disabled" is defined as having a physical or mental disability : unable to perform one or more natural activities (such as walking or seeing) because of illness, injury, etc.

The word disabled came to be used as the standard term in referring to people with physical or mental disabilities in the second half of the 20th century - and it remains the most generally accepted term in both British and US English. Lately, "Disability" and "Disabled" are terms that are undergoing change due to the disability rights movement in the U.S. and U.K. - Disability or Disabled - Which Term is Right?

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Disability is a subject you may read about online, or in a newspaper, but not think of as something that might actually happen to you. But your chances of becoming disabled are greater than you realize. Today more people live with a disability than ever before due to our aging societies as well as improved medical treatments helping manage long-term health problems.

Some people are born with a disability, others become disabled as a result of an illness or injury, and some people develop them as they age. At some point in our lives almost all of us will have some type of disability.

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Spinal Cord Stem Cells Comments Off on Disabled World – Disability News & Information | January 19th, 2017

This article is about birth in humans. For birth in other mammals, see birth.

Childbirth, also known as labour and delivery, is the ending of a pregnancy by one or more babies leaving a woman's uterus.[1] In 2015 there were about 135 million births globally.[2] About 15 million were born before 37 weeks of gestation,[3] while between 3 and 12% were born after 42 weeks.[4] In the developed world most deliveries occur in hospital,[5][6] while in the developing world most births take place at home with the support of a traditional birth attendant.[7]

The most common way of childbirth is a vaginal delivery.[8] It involves three stages of labour: the shortening and opening of the cervix, descent and birth of the baby, and the pushing out of the placenta.[9] The first stage typically lasts twelve to nineteen hours, the second stage twenty minutes to two hours, and the third stage five to thirty minutes.[10] The first stage begins with crampy abdominal or back pains that last around half a minute and occur every ten to thirty minutes.[9] The crampy pains become stronger and closer together over time.[10] During the second stage pushing with contractions may occur.[10] In the third stage delayed clamping of the umbilical cord is generally recommended.[11] A number of methods can help with pain such as relaxation techniques, opioids, and spinal blocks.[10]

Most babies are born head first; however about 4% are born feet or buttock first, known as breech.[10][12] During labour a women can generally eat and move around as she likes, pushing is not recommended during the first stage or during delivery of the head, and enemas are not recommended.[13] While making a cut to the opening of the vagina is common, known as an episiotomy, it is generally not needed.[10] In 2012, about 23 million deliveries occurred by a surgical procedure known as Caesarean section.[14] Caesarean sections may be recommended for twins, signs of distress in the baby, or breech position.[10] This method of delivery can take longer to heal from.[10]

Each year complications from pregnancy and childbirth result in about 500,000 maternal deaths, 7 million women have serious long term problems, and 50 million women have health negative outcomes following delivery.[15] Most of these occur in the developing world.[15] Specific complications include obstructed labour, postpartum bleeding, eclampsia, and postpartum infection.[15] Complications in the baby include birth asphyxia.[16]

The most prominent sign of labour is strong repetitive uterine contractions. The distress levels reported by labouring women vary widely. They appear to be influenced by fear and anxiety levels, experience with prior childbirth, cultural ideas of childbirth and pain,[17][18] mobility during labour, and the support received during labour. Personal expectations, the amount of support from caregivers, quality of the caregiver-patient relationship, and involvement in decision-making are more important in women's overall satisfaction with the experience of childbirth than are other factors such as age, socioeconomic status, ethnicity, preparation, physical environment, pain, immobility, or medical interventions.[19]

Pain in contractions has been described as feeling similar to very strong menstrual cramps. Women are often encouraged to refrain from screaming, but moaning and grunting may be encouraged to help lessen pain. Crowning may be experienced as an intense stretching and burning. Even women who show little reaction to labour pains, in comparison to other women, show a substantially severe reaction to crowning.

Back labour is a term for specific pain occurring in the lower back, just above the tailbone, during childbirth.[20]

Childbirth can be an intense event and strong emotions, both positive and negative, can be brought to the surface. Abnormal and persistent fear of childbirth is known as tokophobia.

During the later stages of gestation there is an increase in abundance of oxytocin, a hormone that is known to evoke feelings of contentment, reductions in anxiety, and feelings of calmness and security around the mate.[21] Oxytocin is further released during labour when the fetus stimulates the cervix and vagina, and it is believed that it plays a major role in the bonding of a mother to her infant and in the establishment of maternal behavior. The act of nursing a child also causes a release of oxytocin.[22]

Between 70% and 80% of mothers in the United States report some feelings of sadness or "baby blues" after giving birth. The symptoms normally occur for a few minutes up to few hours each day and they should lessen and disappear within two weeks after delivery. Postpartum depression may develop in some women; about 10% of mothers in the United States are diagnosed with this condition. Preventive group therapy has proven effective as a prophylactic treatment for postpartum depression.[23][24]

Humans are bipedal with an erect stance. The erect posture causes the weight of the abdominal contents to thrust on the pelvic floor, a complex structure which must not only support this weight but allow, in women, three channels to pass through it: the urethra, the vagina and the rectum. The infant's head and shoulders must go through a specific sequence of maneuvers in order to pass through the ring of the mother's pelvis.

Six phases of a typical vertex (head-first presentation) delivery:

Station refers to the relationship of the fetal presenting part to the level of the ischial spines. When the presenting part is at the ischial spines the station is 0 (synonymous with engagement). If the presenting fetal part is above the spines, the distance is measured and described as minus stations, which range from 1 to 4cm. If the presenting part is below the ischial spines, the distance is stated as plus stations ( +1 to +4cm). At +3 and +4 the presenting part is at the perineum and can be seen.[25]

The fetal head may temporarily change shape substantially (becoming more elongated) as it moves through the birth canal. This change in the shape of the fetal head is called molding and is much more prominent in women having their first vaginal delivery.[26]

There are various definitions of the onset of labour, including:

In order to avail for more uniform terminology, the first stage of labour is divided into "latent" and "active" phases, where the latent phase is sometimes included in the definition of labour,[30] and sometimes not.[31]

Some reports note that the onset of term labour more commonly takes place in the late night and early morning hours. This may be a result of a synergism between the nocturnal increase in melatonin and oxytocin.[32]

The latent phase of labour is also called the quiescent phase, prodromal labour, or pre-labour. It is a subclassification of the first stage.[33]

The latent phase is generally defined as beginning at the point at which the woman perceives regular uterine contractions.[34] In contrast, Braxton Hicks contractions, which are contractions that may start around 26 weeks gestation and are sometimes called "false labour", should be infrequent, irregular, and involve only mild cramping.[35] The signaling mechanisms responsible for uterine coordination are complex. Electrical propagation is the primary mechanism used for signaling up to several centimeters. Over longer distances, however, signaling may involve a mechanical mechanism.[36]

Cervical effacement, which is the thinning and stretching of the cervix, and cervical dilation occur during the closing weeks of pregnancy and is usually complete or near complete, by the end of the latent phase.[citation needed] The degree of cervical effacement may be felt during a vaginal examination. A 'long' cervix implies that effacement has not yet occurred. Latent phase ends with the onset of active first stage, and this transition is defined retrospectively.

The active stage of labour (or "active phase of first stage" if the previous phase is termed "latent phase of first stage") has geographically differing definitions. In the US, the definition of active labour was changed from 3 to 4cm, to 5cm of cervical dilation for multiparous women, mothers who had given birth previously, and at 6cm for nulliparous women, those who had not given birth before.[37] This has been done in an effort to increase the rates of vaginal delivery.[38]

A definition of active labour in a British journal was having contractions more frequent than every 5 minutes, in addition to either a cervical dilation of 3cm or more or a cervical effacement of 80% or more.[39]

In Sweden, the onset of the active phase of labour is defined as when two of the following criteria are met:[40]

Health care providers may assess a labouring mother's progress in labour by performing a cervical exam to evaluate the cervical dilation, effacement, and station. These factors form the Bishop score. The Bishop score can also be used as a means to predict the success of an induction of labour.

During effacement, the cervix becomes incorporated into the lower segment of the uterus. During a contraction, uterine muscles contract causing shortening of the upper segment and drawing upwards of the lower segment, in a gradual expulsive motion.[citation needed] The presenting fetal part then is permitted to descend. Full dilation is reached when the cervix has widened enough to allow passage of the baby's head, around 10cm dilation for a term baby.

The duration of labour varies widely, but the active phase averages some 8 hours[41] for women giving birth to their first child ("primiparae") and shorter for women who have already given birth ("multiparae"). Active phase prolongation is defined as in a primigravid woman as the failure of the cervix to dilate at a rate of 1.2cm/h over a period of at least two hours. This definition is based on Friedman's Curve, which plots the typical rate of cervical dilation and fetal descent during active labour.[42] Some practitioners may diagnose "Failure to Progress", and consequently, propose interventions to optimize chances for healthy outcome.[43]

The expulsion stage (stimulated by prostaglandins and oxytocin) begins when the cervix is fully dilated, and ends when the baby is born. As pressure on the cervix increases, women may have the sensation of pelvic pressure and an urge to begin pushing. At the beginning of the normal second stage, the head is fully engaged in the pelvis; the widest diameter of the head has passed below the level of the pelvic inlet. The fetal head then continues descent into the pelvis, below the pubic arch and out through the vaginal introitus (opening). This is assisted by the additional maternal efforts of "bearing down" or pushing. The appearance of the fetal head at the vaginal orifice is termed the "crowning". At this point, the woman will feel an intense burning or stinging sensation.

When the amniotic sac has not ruptured during labour or pushing, the infant can be born with the membranes intact. This is referred to as "delivery en caul".

Complete expulsion of the baby signals the successful completion of the second stage of labour.

The second stage of birth will vary by factors including parity (the number of children a woman has had), fetal size, anesthesia, and the presence of infection. Longer labours are associated with declining rates of spontaneous vaginal delivery and increasing rates of infection, perineal laceration, and obstetric hemorrhage, as well as the need for intensive care of the neonate.[44]

The period from just after the fetus is expelled until just after the placenta is expelled is called the third stage of labour or the involution stage. Placental expulsion begins as a physiological separation from the wall of the uterus. The average time from delivery of the baby until complete expulsion of the placenta is estimated to be 1012 minutes dependent on whether active or expectant management is employed[45] In as many as 3% of all vaginal deliveries, the duration of the third stage is longer than 30 minutes and raises concern for retained placenta.[46]

Placental expulsion can be managed actively or it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Active management is described as the administration of a uterotonic drug within one minute of fetal delivery, controlled traction of the umbilical cord and fundal massage after delivery of the placenta, followed by performance of uterine massage every 15 minutes for two hours.[47] In a joint statement, World Health Organization, the International Federation of Gynaecology and Obstetrics and the International Confederation of Midwives recommend active management of the third stage of labour in all vaginal deliveries to help to prevent postpartum hemorrhage.[48][49][50]

Delaying the clamping of the umbilical cord until at least one minute after birth improves outcomes as long as there is the ability to treat jaundice if it occurs.[51] In some birthing centers, this may be delayed by 5 minutes or more, or omitted entirely. Delayed clamping of the cord decreases the risk of anemia but may increase risk of jaundice. Clamping is followed by cutting of the cord, which is painless due to the absence of nerves.

The "fourth stage of labour" is the period beginning immediately after the birth of a child and extending for about six weeks. The terms postpartum and postnatal are often used to describe this period.[52] It is the time in which the mother's body, including hormone levels and uterus size, return to a non-pregnant state and the newborn adjusts to life outside the mother's body. The World Health Organization (WHO) describes the postnatal period as the most critical and yet the most neglected phase in the lives of mothers and babies; most deaths occur during the postnatal period.[53]

Following the birth, if the mother had an episiotomy or a tearing of the perineum, it is stitched. The mother should have regular assessments for uterine contraction and fundal height,[54] vaginal bleeding, heart rate and blood pressure, and temperature, for the first 24 hours after birth. The first passing of urine should be documented within 6 hours.[53] Afterpains (pains similar to menstrual cramps), contractions of the uterus to prevent excessive blood flow, continue for several days. Vaginal discharge, termed "lochia", can be expected to continue for several weeks; initially bright red, it gradually becomes pink, changing to brown, and finally to yellow or white.[55]

Most authorities suggest the infant be placed in skin-to-skin contact with the mother for 1 2 hours immediately after birth, putting routine cares off till later.

Until recently babies born in hospitals were removed from their mothers shortly after birth and brought to the mother only at feeding times. Mothers were told that their newborn would be safer in the nursery and that the separation would offer the mother more time to rest. As attitudes began to change, some hospitals offered a "rooming in" option wherein after a period of routine hospital procedures and observation, the infant could be allowed to share the mother's room. However, more recent information has begun to question the standard practice of removing the newborn immediately postpartum for routine postnatal procedures before being returned to the mother. Beginning around 2000, some authorities began to suggest that early skin-to-skin contact (placing the naked baby on the mother's chest) may benefit both mother and infant. Using animal studies that have shown that the intimate contact inherent in skin-to-skin contact promotes neurobehaviors that result in the fulfillment of basic biological needs as a model, recent studies have been done to assess what, if any, advantages may be associated with early skin-to-skin contact for human mothers and their babies. A 2011 medical review looked at existing studies and found that early skin-to-skin contact, sometimes called kangaroo care, resulted in improved breastfeeding outcomes, cardio-respiratory stability, and a decrease in infant crying. [56][57][58] A 2007 Cochrane review of studies found that skin-to-skin contact at birth reduced crying, kept the baby warmer, improved mother-baby interaction, and improved the chances for successful breastfeeding.[59]

As of 2014, early postpartum skin-to-skin contact is endorsed by all major organizations that are responsible for the well-being of infants, including the American Academy of Pediatrics.[60] The World Health Organization (WHO) states that "the process of childbirth is not finished until the baby has safely transferred from placental to mammary nutrition." They advise that the newborn be placed skin-to-skin with the mother, postponing any routine procedures for at least one to two hours. The WHO suggests that any initial observations of the infant can be done while the infant remains close to the mother, saying that even a brief separation before the baby has had its first feed can disturb the bonding process. They further advise frequent skin-to-skin contact as much as possible during the first days after delivery, especially if it was interrupted for some reason after the delivery.[61] The National Institute for Health and Care Excellence also advises postponing procedures such as weighing, measuring, and bathing for at least 1 hour to insure an initial period of skin-to-skin contact between mother and infant. [62]

Deliveries are assisted by a number of professions include: obstetricians, family physicians and midwives. For low risk pregnancies all three result in similar outcomes.[63]

Eating or drinking during labour is an area of ongoing debate. While some have argued that eating in labour has no harmful effects on outcomes,[64] others continue to have concern regarding the increased possibility of an aspiration event (choking on recently eaten foods) in the event of an emergency delivery due to the increased relaxation of the esophagus in pregnancy, upward pressure of the uterus on the stomach, and the possibility of general anesthetic in the event of an emergency cesarean.[65] A 2013 Cochrane review found that with good obstetrical anaesthesia there is no change in harms from allowing eating and drinking during labour in those who are unlikely to need surgery. They additionally acknowledge that not eating does not mean there is an empty stomach or that its contents are not as acidic. They therefore conclude that "women should be free to eat and drink in labour, or not, as they wish."[66]

At one time shaving of the area around the vagina, was common practice due to the belief that hair removal reduced the risk of infection, made an episiotomy (a surgical cut to enlarge the vaginal entrance) easier, and helped with instrumental deliveries. It is currently less common, though it is still a routine procedure in some countries. A 2009 Cochrane review found no evidence of any benefit with perineal shaving. The review did find side effects including irritation, redness, and multiple superficial scratches from the razor.[67][needs update] Another effort to prevent infection has been the use of the antiseptic chlorhexidine or providone-iodine solution in the vagina. Evidence of benefit with chlorhexidine is lacking.[68] A decreased risk is found with providone-iodine when a cesarean section is to be performed.[69]

Active management of labour consists of a number of care principles, including frequent assessment of cervical dilatation. If the cervix is not dilating, oxytocin is offered. This management results in a slightly reduced number of caesarean births, but does not change how many women have assisted vaginal births. 75% of women report that they are very satisfied with either active management or normal care.[70]

In many cases and with increasing frequency, childbirth is achieved through induction of labour or caesarean section. Caesarean section is the removal of the neonate through a surgical incision in the abdomen, rather than through vaginal birth.[71] Childbirth by C-Sections increased 50% in the U.S. from 1996 to 2006, and comprise nearly 32% of births in the U.S. and Canada.[71][72] Induced births and elective cesarean before 39 weeks can be harmful to the neonate as well as harmful or without benefit to the mother. Therefore, many guidelines recommend against non-medically required induced births and elective cesarean before 39 weeks.[73] The rate of labour induction in the United States is 22%, and has more than doubled from 1990 to 2006.[74][75]

Health conditions that may warrant induced labour or cesarean delivery include gestational or chronic hypertension, preeclampsia, eclampsia, diabetes, premature rupture of membranes, severe fetal growth restriction, and post-term pregnancy. Cesarean section too may be of benefit to both the mother and baby for certain indications including maternal HIV/AIDS, fetal abnormality, breech position, fetal distress, multiple gestations, and maternal medical conditions which would be worsened by labour or vaginal birth.

Pitocin is the most commonly used agent for induction in the United States, and is used to induce uterine contractions. Other methods of inducing labour include stripping of the amniotic membrane, artificial rupturing of the amniotic sac (called amniotomy), or nipple stimulation. Ripening of the cervix can be accomplished with the placement of a Foley catheter or the use of synthetic prostaglandins such as misoprostol.[74] A large review of methods of induction was published in 2011.[76]

The American Congress of Obstetricians and Gynecologists (ACOG) guidelines recommend a full evaluation of the maternal-fetal status, the status of the cervix, and at least a 39 completed weeks (full term) of gestation for optimal health of the newborn when considering elective induction of labour. Per these guidelines, the following conditions may be an indication for induction, including:

Induction is also considered for logistical reasons, such as the distance from hospital or psychosocial conditions, but in these instances gestational age confirmation must be done, and the maturity of the fetal lung must be confirmed by testing.

The ACOG also note that contraindications for induced labour are the same as for spontaneous vaginal delivery, including vasa previa, complete placenta praevia, umbilical cord prolapse or active genital herpes simplex infection.[77]

Some women prefer to avoid analgesic medication during childbirth. Psychological preparation may be beneficial. A recent Cochrane overview of systematic reviews on non-drug interventions found that relaxation techniques, immersion in water, massage, and acupuncture may provide pain relief. Acupuncture and relaxation were found to decrease the number of caesarean sections required.[78] Immersion in water has been found to relieve pain during the first stage of labor and to reduce the need for anesthesia and shorten the duration of labor, however the safety and efficacy of immersion during birth, water birth, has not been established or associated with maternal or fetal benefit.[79]

Some women like to have someone to support them during labour and birth; such as a midwife, nurse, or doula; or a lay person such as the father of the baby, a family member, or a close friend. Studies have found that continuous support during labor and delivery reduce the need for medication and a caesarean or operative vaginal delivery, and result in an improved Apgar score for the infant.[80][81]

The injection of small amounts of sterile water into or just below the skin at several points on the back has been a method tried to reduce labour pain, but no good evidence shows that it actually helps.[82]

Different measures for pain control have varying degrees of success and side effects to the woman and her baby. In some countries of Europe, doctors commonly prescribe inhaled nitrous oxide gas for pain control, especially as 53% nitrous oxide, 47% oxygen, known as Entonox; in the UK, midwives may use this gas without a doctor's prescription. Opioids such as fentanyl may be used, but if given too close to birth there is a risk of respiratory depression in the infant.

Popular medical pain control in hospitals include the regional anesthetics epidurals (EDA), and spinal anaesthesia. Epidural analgesia is a generally safe and effective method of relieving pain in labour, but is associated with longer labour, more operative intervention (particularly instrument delivery), and increases in cost.[83] Generally, pain and stress hormones rise throughout labour for women without epidurals, while pain, fear, and stress hormones decrease upon administration of epidural analgesia, but rise again later.[84] Medicine administered via epidural can cross the placenta and enter the bloodstream of the fetus.[85] Epidural analgesia has no statistically significant impact on the risk of caesarean section, and does not appear to have an immediate effect on neonatal status as determined by Apgar scores.[86]

Augmentation is the process of facilitating further labour. Oxytocin has been used to increase the rate of vaginal delivery in those with a slow progress of labour.[87]

Administration of antispasmodics (e.g. hyoscine butylbromide) is not formally regarded as augmentation of labour; however, there is weak evidence that they may shorten labour.[88] There is not enough evidence to make conclusions about unwanted effects in mothers or babies.[88]

Vaginal tears can occur during childbirth, most often at the vaginal opening as the baby's head passes through, especially if the baby descends quickly. Tears can involve the perineal skin or extend to the muscles and the anal sphincter and anus. The midwife or obstetrician may decide to make a surgical cut to the perineum (episiotomy) to make the baby's birth easier and prevent severe tears that can be difficult to repair. A 2012 Cochrane review compared episiotomy as needed (restrictive) with routine episiotomy to determine the possible benefits and harms for mother and baby. The review found that restrictive episiotomy policies appeared to give a number of benefits compared with using routine episiotomy. Women experienced less severe perineal trauma, less posterior perineal trauma, less suturing and fewer healing complications at seven days with no difference in occurrence of pain, urinary incontinence, painful sex or severe vaginal/perineal trauma after birth, however they found that women experienced more anterior perineal damage with restrictive episiotomy.[89]

Obstetric forceps or ventouse may be used to facilitate childbirth.

In cases of a cephalic presenting twin (first baby head down), twins can often be delivered vaginally. In some cases twin delivery is done in a larger delivery room or in an operating theatre, in the event of complication e.g.

Historically women have been attended and supported by other women during labour and birth. However currently, as more women are giving birth in a hospital rather than at home, continuous support has become the exception rather than the norm. When women became pregnant any time before the 1950s the husband would not be in the birthing room. It did not matter if it was a home birth; the husband was waiting downstairs or in another room in the home. If it was in a hospital then the husband was in the waiting room. "Her husband was attentive and kind, but, Kirby concluded, Every good woman needs a companion of her own sex."[90] Obstetric care frequently subjects women to institutional routines, which may have adverse effects on the progress of labour. Supportive care during labour may involve emotional support, comfort measures, and information and advocacy which may promote the physical process of labour as well as women's feelings of control and competence, thus reducing the need for obstetric intervention. The continuous support may be provided either by hospital staff such as nurses or midwives, doulas, or by companions of the woman's choice from her social network. There is increasing evidence to show that the participation of the child's father in the birth leads to better birth and also post-birth outcomes, providing the father does not exhibit excessive anxiety.[91]

A recent Cochrane review involving more than 15,000 women in a wide range of settings and circumstances found that "Women who received continuous labour support were more likely to give birth 'spontaneously', i.e. give birth with neither caesarean nor vacuum nor forceps. In addition, women were less likely to use pain medications, were more likely to be satisfied, and had slightly shorter labours. Their babies were less likely to have low five-minute Apgar scores."[80]

For monitoring of the fetus during childbirth, a simple pinard stethoscope or doppler fetal monitor ("doptone") can be used. A method of external (noninvasive) fetal monitoring (EFM) during childbirth is cardiotocography, using a cardiotocograph that consists of two sensors: The heart (cardio) sensor is an ultrasonic sensor, similar to a Doppler fetal monitor, that continuously emits ultrasound and detects motion of the fetal heart by the characteristic of the reflected sound. The pressure-sensitive contraction transducer, called a tocodynamometer (toco) has a flat area that is fixated to the skin by a band around the belly. The pressure required to flatten a section of the wall correlates with the internal pressure, thereby providing an estimate of contraction[92] Monitoring with a cardiotocograph can either be intermittent or continuous.

A mother's water has to break before internal (invasive) monitoring can be used. More invasive monitoring can involve a fetal scalp electrode to give an additional measure of fetal heart activity, and/or intrauterine pressure catheter (IUPC). It can also involve fetal scalp pH testing.

It is currently possible to collect two types of stem cells during childbirth: amniotic stem cells and umbilical cord blood stem cells.[93] They are being studied as possible treatments of a number of conditions.[93]

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The "natural" maternal mortality rate of childbirthwhere nothing is done to avert maternal deathhas been estimated at 1500 deaths per 100,000 births.[95] (See main articles: neonatal death, maternal death). Each year about 500,000 women die due to pregnancy, 7 million have serious long term complications, and 50 million have negative outcomes following delivery.[15]

Modern medicine has decreased the risk of childbirth complications. In Western countries, such as the United States and Sweden, the current maternal mortality rate is around 10 deaths per 100,000 births.[95]:p.10 As of June 2011, about one third of American births have some complications, "many of which are directly related to the mother's health."[96]

Birthing complications may be maternal or fetal, and long term or short term.

Newborn mortality at 37 weeks may be 2.5 times the number at 40 weeks, and was elevated compared to 38 weeks of gestation. These "early term" births were also associated with increased death during infancy, compared to those occurring at 39 to 41 weeks ("full term").[73] Researchers found benefits to going full term and "no adverse effects" in the health of the mothers or babies.[73]

Medical researchers find that neonates born before 39 weeks experienced significantly more complications (2.5 times more in one study) compared with those delivered at 39 to 40 weeks. Health problems among babies delivered "pre-term" included respiratory distress, jaundice and low blood sugar.[73][97] The American Congress of Obstetricians and Gynecologists and medical policy makers review research studies and find increased incidence of suspected or proven sepsis, RDS, Hypoglycemia, need for respiratory support, need for NICU admission, and need for hospitalization > 4 5 days. In the case of cesarean sections, rates of respiratory death were 14 times higher in pre-labour at 37 compared with 40 weeks gestation, and 8.2 times higher for pre-labour cesarean at 38 weeks. In this review, no studies found decreased neonatal morbidity due to non-medically indicated (elective) delivery before 39 weeks.[73]

The second stage of labour may be delayed or lengthy due to:

Secondary changes may be observed: swelling of the tissues, maternal exhaustion, fetal heart rate abnormalities. Left untreated, severe complications include death of mother and/or baby, and genitovaginal fistula.

Obstructed labour, also known as labor dystocia, is when, even though the uterus is contracting normally, the baby does not exit the pelvis during childbirth due to being physically blocked.[98] Prolonged obstructed labor can result in obstetric fistula, a complication of childbirth where tissue death preforates the rectum or bladder.

Vaginal birth injury with visible tears or episiotomies are common. Internal tissue tearing as well as nerve damage to the pelvic structures lead in a proportion of women to problems with prolapse, incontinence of stool or urine and sexual dysfunction. Fifteen percent of women become incontinent, to some degree, of stool or urine after normal delivery, this number rising considerably after these women reach menopause. Vaginal birth injury is a necessary, but not sufficient, cause of all non hysterectomy related prolapse in later life. Risk factors for significant vaginal birth injury include:

There is tentative evidence that antibiotics may help prevent wound infections in women with third or fourth degree tears.[99]

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Childbirth - Wikipedia

Spinal Cord Stem Cells Comments Off on Childbirth – Wikipedia | January 13th, 2017

The central nervous system (CNS) is the part of the nervous system consisting of the brain and spinal cord. The central nervous system is so named because it integrates information it receives from, and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animalsthat is, all multicellular animals except sponges and radially symmetric animals such as jellyfishand it contains the majority of the nervous system. Many consider the retina[2] and the optic nerve (2nd cranial nerve),[3][4] as well as the olfactory nerves (1st) and olfactory epithelium[5] as parts of the CNS, synapsing directly on brain tissue without intermediate ganglia. Following this classification[which?] the olfactory epithelium is the only central nervous tissue in direct contact with the environment, which opens up for therapeutic treatments. [5] The CNS is contained within the dorsal body cavity, with the brain housed in the cranial cavity and the spinal cord in the spinal canal. In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae, both enclosed in the meninges.[6]

The central nervous system consists of the two major structures: the brain and spinal cord. The brain is encased in the skull, and protected by the cranium.[7] The spinal cord is continuous with the brain and lies caudally to the brain,[8] and is protected by the vertebra.[7] The spinal cord reaches from the base of the skull, continues through[7] or starting below[9] the foramen magnum,[7] and terminates roughly level with the first or second lumbar vertebra,[8][9] occupying the upper sections of the vertebral canal.[4]

Microscopically, there are differences between the neurons and tissue of the central nervous system and the peripheral nervous system.[citation needed] The central nervous system is divided in white and gray matter.[8] This can also be seen macroscopically on brain tissue. The white matter consists of axons and oligodendrocytes, while the gray matter consists of neurons and unmyelinated fibers. Both tissues include a number of glial cells (although the white matter contains more), which are often referred to as supporting cells of the central nervous system. Different forms of glial cells have different functions, some acting almost as scaffolding for neuroblasts to climb during neurogenesis such as bergmann glia, while others such as microglia are a specialized form of macrophage, involved in the immune system of the brain as well as the clearance of various metabolites from the brain tissue.[4]Astrocytes may be involved with both clearance of metabolites as well as transport of fuel and various beneficial substances to neurons from the capillaries of the brain. Upon CNS injury astrocytes will proliferate, causing gliosis, a form of neuronal scar tissue, lacking in functional neurons.[4]

The brain (cerebrum as well as midbrain and hindbrain) consists of a cortex, composed of neuron-bodies constituting gray matter, while internally there is more white matter that form tracts and commissures. Apart from cortical gray matter there is also subcortical gray matter making up a large number of different nuclei.[8]

From and to the spinal cord are projections of the peripheral nervous system in the form of spinal nerves (sometimes segmental nerves[7]). The nerves connect the spinal cord to skin, joints, muscles etc. and allow for the transmission of efferent motor as well as afferent sensory signals and stimuli.[8] This allows for voluntary and involuntary motions of muscles, as well as the perception of senses. All in all 31 spinal nerves project from the brain stem,[8] some forming plexa as they branch out, such as the brachial plexa, sacral plexa etc.[7] Each spinal nerve will carry both sensory and motor signals, but the nerves synapse at different regions of the spinal cord, either from the periphery to sensory relay neurons that relay the information to the CNS or from the CNS to motor neurons, which relay the information out.[8]

The spinal cord relays information up to the brain through spinal tracts through the "final common pathway"[8] to the thalamus and ultimately to the cortex. Not all information is relayed to the cortex, and does not reach our immediate consciousness, but is instead transmitted only to the thalamus which sorts and adapts accordingly. This in turn may explain why we are not constantly aware of all aspects of our surroundings.[citation needed]

Schematic image showing the locations of a few tracts of the spinal cord.

Reflexes may also occur without engaging more than one neuron of the central nervous system as in the below example of a short reflex.

Apart from the spinal cord, there are also peripheral nerves of the PNS that synapse through intermediaries or ganglia directly on the CNS. These 12 nerves exist in the head and neck region and are called cranial nerves. Cranial nerves bring information to the CNS to and from the face, as well as to certain muscles (such as the trapezius muscle, which is innervated by accessory nerves[7] as well as certain cervical spinal nerves).[7]

Two pairs of cranial nerves; the olfactory nerves and the optic nerves[2] are often considered structures of the central nervous system. This is because they do not synapse first on peripheral ganglia, but directly on central nervous neurons. The olfactory epithelium is significant in that it consists of central nervous tissue expressed in direct contact to the environment, allowing for administration of certain pharmaceuticals and drugs. [5]

Myelinated peripheral nerve at top, central nervous neuron at bottom

Rostrally to the spinal cord lies the brain.[8] The brain makes up the largest portion of the central nervous system, and is often the main structure referred to when speaking of the nervous system. The brain is the major functional unit of the central nervous system. While the spinal cord has certain processing ability such as that of spinal locomotion and can process reflexes, the brain is the major processing unit of the nervous system.[citation needed]

The brainstem consists of the medulla, the pons and the midbrain. The medulla can be referred to as an extension of the spinal cord, and its organization and functional properties are similar to those of the spinal cord.[8] The tracts passing from the spinal cord to the brain pass through here.[8]

Regulatory functions of the medulla nuclei include control of the blood pressure and breathing. Other nuclei are involved in balance, taste, hearing and control of muscles of the face and neck.[8]

The next structure rostral to the medulla is the pons, which lies on the ventral anterior side of the brainstem. Nuclei in the pons include pontine nuclei which work with the cerebellum and transmit information between the cerebellum and the cerebral cortex.[8] In the dorsal posterior pons lie nuclei that have to do with breathing, sleep and taste.[8]

The midbrain (or mesencephalon) is situated above and rostral to the pons, and includes nuclei linking distinct parts of the motor system, among others the cerebellum, the basal ganglia and both cerebral hemispheres. Additionally parts of the visual and auditory systems are located in the mid brain, including control of automatic eye movements.[8]

The brainstem at large provides entry and exit to the brain for a number of pathways for motor and autonomic control of the face and neck through cranial nerves,[8] and autonomic control of the organs is mediated by the tenth cranial (vagus) nerve.[4] A large portion of the brainstem is involved in such autonomic control of the body. Such functions may engage the heart, blood vessels, pupillae, among others.[8]

The brainstem also hold the reticular formation, a group of nuclei involved in both arousal and alertness.[8]

The cerebellum lies behind the pons. The cerebellum is composed of several dividing fissures and lobes. Its function includes the control of posture, and the coordination of movements of parts of the body, including the eyes and head as well as the limbs. Further it is involved in motion that has been learned and perfected though practice, and will adapt to new learned movements.[8] Despite its previous classification as a motor structure, the cerebellum also displays connections to areas of the cerebral cortex involved in language as well as cognitive functions. These connections have been shown by the use of medical imaging techniques such as fMRI and PET.[8]

The body of the cerebellum holds more neurons than any other structure of the brain including that of the larger cerebrum (or cerebral hemispheres), but is also more extensively understood than other structures of the brain, and includes fewer types of different neurons.[8] It handles and processes sensory stimuli, motor information as well as balance information from the vestibular organ.[8]

The two structures of the diencephalon worth noting are the thalamus and the hypothalamus. The thalamus acts as a linkage between incoming pathways from the peripheral nervous system as well as the optical nerve (though it does not receive input from the olfactory nerve) to the cerebral hemispheres. Previously it was considered only a "relay station", but it is engaged in the sorting of information that will reach cerebral hemispheres (neocortex).[8]

Apart from its function of sorting information from the periphery, the thalamus also connects the cerebellum and basal ganglia with the cerebrum. In common with the aforementioned reticular system the thalamus is involved in wakefullness and consciousness, such as though the SCN.[8]

The hypothalamus engages in functions of a number of primitive emotions or feelings such as hunger, thirst and maternal bonding. This is regulated partly through control of secretion of hormones from the pituitary gland. Additionally the hypothalamus plays a role in motivation and many other behaviors of the individual.[8]

The cerebrum of cerebral hemispheres make up the largest visual portion of the human brain. Various structures combine forming the cerebral hemispheres, among others, the cortex, basal ganglia, amygdala and hippocampus. The hemispheres together control a large portion of the functions of the human brain such as emotion, memory, perception and motor functions. Apart from this the cerebral hemispheres stand for the cognitive capabilities of the brain.[8]

Connecting each of the hemispheres is the corpus callosum as well as several additional commissures.[8] One of the most important parts of the cerebral hemispheres is the cortex, made up of gray matter covering the surface of the brain. Functionally, the cerebral cortex is involved in planning and carrying out of everyday tasks.[8]

The hippocampus is involved in storage of memories, the amygdala plays a role in perception and communication of emotion, while the basal ganglia play a major role in the coordination of voluntary movement.[8]

This differentiates the central nervous system from the peripheral nervous system, which consists of neurons, axons and Schwann cells. Oligodendrocytes and Schwann cells have similar functions in the central and peripheral nervous system respectively. Both act to add myelin sheaths to the axons, which acts as a form of insulation allowing for better and faster proliferation of electrical signals along the nerves. Axons in the central nervous system are often very short (barely a few millimeters) and do not need the same degree of isolation as peripheral nerves do. Some peripheral nerves can be over 1m in length, such as the nerves to the big toe. To ensure signals move at sufficient speed, myelination is needed.

The way in which the Schwann cells and oligodendrocytes myelinate nerves differ. A Schwann cell usually myelinates a single axon, completely surrounding it. Sometimes they may myelinate many axons, especially when in areas of short axons.[7] Oligodendrocytes usually myelinate several axons. They do this by sending out thin projections of their cell membrane which envelop and enclose the axon.

Top; CNS as seen in a median section of a 5 week old embryo. Bottom; CNS seen in a median section of a 3 month old embryo.

During early development of the vertebrate embryo, a longitudinal groove on the neural plate gradually deepens and the ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube called the neural tube.[10] The formation of the neural tube is called neurulation. At this stage, the walls of the neural tube contain proliferating neural stem cells in a region called the ventricular zone. The neural stem cells, principally radial glial cells, multiply and generate neurons through the process of neurogenesis, forming the rudiment of the central nervous system.[11]

The neural tube gives rise to both brain and spinal cord. The anterior (or 'rostral') portion of the neural tube initially differentiates into three brain vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon; and the rhombencephalon divides into the metencephalon and myelencephalon. The spinal cord is derived from the posterior or 'caudal' portion of the neural tube.

As a vertebrate grows, these vesicles differentiate further still. The telencephalon differentiates into, among other things, the striatum, the hippocampus and the neocortex, and its cavity becomes the first and second ventricles. Diencephalon elaborations include the subthalamus, hypothalamus, thalamus and epithalamus, and its cavity forms the third ventricle. The tectum, pretectum, cerebral peduncle and other structures develop out of the mesencephalon, and its cavity grows into the mesencephalic duct (cerebral aqueduct). The metencephalon becomes, among other things, the pons and the cerebellum, the myelencephalon forms the medulla oblongata, and their cavities develop into the fourth ventricle.[12]

Development of the neural tube

Rhinencephalon, Amygdala, Hippocampus, Neocortex, Basal ganglia, Lateral ventricles

Epithalamus, Thalamus, Hypothalamus, Subthalamus, Pituitary gland, Pineal gland, Third ventricle

Tectum, Cerebral peduncle, Pretectum, Mesencephalic duct

Pons, Cerebellum

Planarians, members of the phylum Platyhelminthes (flatworms), have the simplest, clearly defined delineation of a nervous system into a central nervous system (CNS) and a peripheral nervous system (PNS).[13][14] Their primitive brains, consisting of two fused anterior ganglia, and longitudinal nerve cords form the CNS; the laterally projecting nerves form the PNS. A molecular study found that more than 95% of the 116 genes involved in the nervous system of planarians, which includes genes related to the CNS, also exist in humans.[15] Like planarians, vertebrates have a distinct CNS and PNS, though more complex than those of planarians.

In arthropods, the ventral nerve cord, the subesophageal ganglia and the supraesophageal ganglia are usually seen as making up the CNS.

The CNS of chordates differs from that of other animals in being placed dorsally in the body, above the gut and notochord/spine.[16] The basic pattern of the CNS is highly conserved throughout the different species of vertebrates and during evolution. The major trend that can be observed is towards a progressive telencephalisation: the telencephalon of reptiles is only an appendix to the large olfactory bulb, while in mammals it makes up most of the volume of the CNS. In the human brain, the telencephalon covers most of the diencephalon and the mesencephalon. Indeed, the allometric study of brain size among different species shows a striking continuity from rats to whales, and allows us to complete the knowledge about the evolution of the CNS obtained through cranial endocasts.

Mammals which appear in the fossil record after the first fishes, amphibians, and reptiles are the only vertebrates to possess the evolutionarily recent, outermost part of the cerebral cortex known as the neocortex.[17] The neocortex of monotremes (the duck-billed platypus and several species of spiny anteaters) and of marsupials (such as kangaroos, koalas, opossums, wombats, and Tasmanian devils) lack the convolutions gyri and sulci found in the neocortex of most placental mammals (eutherians).[18] Within placental mammals, the size and complexity of the neocortex increased over time. The area of the neocortex of mice is only about 1/100 that of monkeys, and that of monkeys is only about 1/10 that of humans.[17] In addition, rats lack convolutions in their neocortex (possibly also because rats are small mammals), whereas cats have a moderate degree of convolutions, and humans have quite extensive convolutions.[17] Extreme convolution of the neocortex is found in dolphins, possibly related to their complex echolocation.

There are many central nervous system diseases and conditions, including infections of the central nervous system such as encephalitis and poliomyelitis, early-onset neurological disorders including ADHD and autism, late-onset neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and essential tremor, autoimmune and inflammatory diseases such as multiple sclerosis and acute disseminated encephalomyelitis, genetic disorders such as Krabbe's disease and Huntington's disease, as well as amyotrophic lateral sclerosis and adrenoleukodystrophy. Lastly, cancers of the central nervous system can cause severe illness and, when malignant, can have very high mortality rates.

Specialty professional organizations recommend that neurological imaging of the brain be done only to answer a specific clinical question and not as routine screening.[19]

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Central nervous system - Wikipedia

Spinal Cord Stem Cells Comments Off on Central nervous system – Wikipedia | January 11th, 2017

Pia mater ( or [1]), often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. Pia mater is medieval Latin meaning "tender mother".[1] The other two meningeal membranes are the dura mater and the arachnoid mater. Both the pia and arachnoid mater are derivatives of the neural crest while the dura is derived from embryonic mesoderm. Pia mater is a thin fibrous tissue that is impermeable to fluid. This allows the pia mater to enclose cerebrospinal fluid. By containing this fluid the pia mater works with the other meningeal layers to protect and cushion the brain. The pia mater allows blood vessels to pass through and nourish the brain. The perivascular space created between blood vessels and pia mater functions as a lymphatic system for the brain. When the pia mater becomes irritated and inflamed the result is meningitis.[2]

Pia mater is the thin, translucent, mesh-like meningeal envelope, spanning nearly the entire surface of the brain. It is absent only at the natural openings between the ventricles, the median aperture, and the lateral aperture. The pia firmly adheres to the surface of the brain and loosely connects to the arachnoid layer.[3] Because of this continuum, the layers are often referred to as the pia arachnoid or leptomeninges. A subarachnoid space exists between the arachnoid layer and the pia, into which the choroid plexus releases and maintains the cerebrospinal fluid (CSF). The subarachnoid space contains trabeculae, or fibrous filaments, that connect and bring stability to the two layers, allowing for the appropriate protection from and movement of the proteins, electrolytes, ions, and glucose contained within the CSF.[4] Romanian biologist Viorel Pais, through recent electron microscopy studies, has demonstrated for the first time in the specialty literature that pia mater is formed by cordocytes and blood vessels.

The thin membrane is composed of fibrous connective tissue, which is covered by a sheet of flat cells impermeable to fluid on its outer surface. A network of blood vessels travels to the brain and spinal cord by interlacing through the pia membrane. These capillaries are responsible for nourishing the brain.[5] This vascular membrane is held together by areolar tissue covered by mesothelial cells from the delicate strands of connective tissue called the arachnoid trabeculae. In the perivascular spaces, the pia mater begins as mesothelial lining on the outer surface, but the cells then fade to be replaced by neuroglia elements.[6]

Although the pia mater is primarily structurally similar throughout, it spans both the spinal cords neural tissue and runs down the fissures of the cerebral cortex in the brain. It is often broken down into two categories, the cranial pia mater (pia mater encephali) and the spinal pia mater (pia mater spinalis).

The section of the pia mater enveloping the brain is known as the cranial pia mater. It is anchored to the brain by the processes of astrocytes, which are glial cells responsible for many functions, including maintenance of the extracellular space. The cranial pia mater joins with the ependyma, which lines the cerebral ventricles to form choroid plexuses that produce cerebrospinal fluid. Together with the other meningeal layers, the function of the pia mater is to protect the central nervous system by containing the cerebrospinal fluid, which cushions the brain and spine.[4]

The cranial pia mater covers the surface of the brain. This layer goes in between the cerebral gyri and cerebellar laminae, folding inward to create the tela chorioidea of the third ventricle and the choroid plexuses of the lateral and third ventricles. At the level of the cerebellum, the pia mater membrane is more fragile due to the length of blood vessels as well as decreased connection to the cerebral cortex.[6]

The spinal pia mater closely follows and encloses the curves of the spinal cord, and is attached to it through a connection to the anterior fissure. The pia mater attaches to the dura mater through 21 pairs of denticulate ligaments that pass through the arachnoid mater and dura mater of the spinal cord. These denticular ligaments help to anchor the spinal cord and prevent side to side movement, providing stability.[7] The membrane in this area is much thicker than the cranial pia mater, due to the two-layer composition of the pia membrane. The outer layer, which is made up of mostly connective tissue, is responsible for this thickness. Between the two layers are spaces which exchange information with the subarachnoid cavity as well as blood vessels. At the point where the pia mater reaches the conus medullaris or medullary cone at the end of the spinal cord, the membrane extends as a thin filament called the filum terminale or terminal filum, contained within the lumbar cistern. This filament eventually blends with the dura mater and extends as far as the coccyx, or tailbone. It then fuses with the periosteum, a membrane found at the surface of all bones, and forms the coccygeal ligament. There it is called the central ligament and assists with movements of the trunk of the body.[6]

In conjunction with the other meningeal membranes, pia mater functions to cover and protect the central nervous system (CNS), to protect the blood vessels and enclose the venous sinuses near the CNS, to contain the cerebrospinal fluid (CSF) and to form partitions with the skull.[8] The CSF, pia mater, and other layers of the meninges work together as a protection device for the brain, with the CSF often referred to as the fourth layer of the meninges.

Cerebrospinal fluid is circulated through the ventricles, cisterns, and subarachnoid space within the brain and spinal cord. About 150mL of CSF is always in circulation, constantly being recycled through the daily production of nearly 500mL of fluid. The CSF is primarily secreted by the choroid plexus; however, about one-third of the CSF is secreted by pia mater and the other ventricular ependymal surfaces (the thin epithelial membrane lining the brain and spinal cord canal) and arachnoidal membranes. The CSF travels from the ventricles and cerebellum through three foramina in the brain, emptying into the cerebrum, and ending its cycle in the venous blood via structures like the arachnoid granulations. The pia spans every surface crevice of the brain other than the foramina to allow the circulation of CSF to continue.[9]

Pia mater allows for the formation of perivascular spaces that help serve as the brains lymphatic system. Blood vessels that penetrate the brain first pass across the surface and then go inwards toward the brain. This direction of flow leads to a layer of the pia mater being carried inwards and loosely adhering to the vessels, leading to the production of a space, namely a perivascular space, between the pia mater and each blood vessel. This is critical because the brain lacks a true lymphatic system. In the remainder of the body, small amounts of protein are able to leak from the parenchymal capillaries through the lymphatic system. In the brain, this ends up in the interstitial space. The protein portions are able to leave through the very permeable pia mater and enter the subarachnoid space in order to flow in the cerebrospinal fluid (CSF), eventually ending up in the cerebral veins. The pia mater serves to create these perivascular spaces to allow passage of certain material, such as fluids, proteins, and even extraneous particulate matter such as dead white blood cells from the blood stream to the CSF, and essentially the brain.[9]

A function of the pia mater is that of the bloodbrain barrier (BBB), which keeps the CSF and brain fluid separate from the blood, allowing limited sodium, chlorine, and potassium through, and absolutely no plasma proteins nor organic molecules. Nearby, the ventricles are lined with the ependyma membrane. The CSF is only kept separate through the pia mater. Due to the ependyma and pia maters high permeability, nearly anything entering the CSF is able to enter the brain interstitial fluid.[9] However, regulation of this permeability is achieved through the abundant amount of astrocyte foot processes which are responsible for connecting the capillaries and the pia mater in a way that helps limit the amount of free diffusion going into the CNS.[10] The permeability of the pia then serves to closely connect the interstitial brain fluid and the CSF and allow them to remain nearly homogenous in terms of composition.[9]

The function of the pia mater is more simply visualized through these ordinary occurrences. This last property is evident in cases of head injury. When the head comes into contact with another object, the brain is protected from the skull due to the similarity in density between these two fluids so that the brain does not simply smash through into the skull, but rather its movement is slowed and stopped by the viscous ability of this fluid. The contrast in permeability between the BBB and pia mater mentioned before is also useful in the application of medicine. Drugs that enter the blood stream can not penetrate and function in the brain, but instead must be administered into the cerebrospinal fluid.[9]

The pia mater also functions to deal with the deformation of the spinal cord under compression. Due to the high elastic modulus of the pia mater, it is able to provide a constraint on the surface of the spinal cord. This constraint stops the elongation of the spinal cord, as well as providing a high strain energy. This high strain energy is useful and responsible for the restoration of the spinal cord to its original shape following a period of decompression.[11]

Ventral root afferents are unmyelinated sensory axons located within the pia mater. These ventral root afferents relay sensory information from the pia mater and allow for the transmission of pain from disc herniation and other spinal injury.[12]

The significant increase in the size of the cerebral hemisphere through evolution has been made possible in part through the evolution of the vascular pia mater, which allows nutrient blood vessels to penetrate deep into the intertwined cerebral matter, providing the necessary nutrients in this larger neural mass. Throughout the course of life on earth, the nervous system of animals has continued to evolve to a more compact and increased organization of neurons and other nervous system cells. This process is most evident in vertebrates and especially mammals in which the increased size of the brain is generally condensed into a smaller space through the presence of sulci or fissures on the surface of the hemisphere divided into gyri allowing more superficies of the cortical grey matter to exist. The development of the meninges and the existence of a defined pia mater was first noted in the vertebrates, and has been more and more significant membrane in the brains of mammals with larger brains.[13]

Meningitis is the inflammation of the pia and arachnoid mater. This is often due to bacteria that have entered the subarachnoid space, but can also be caused by viruses, fungi, as well as non-infectious causes such as certain drugs. It is believed that bacterial meningitis is caused by bacteria that enter the central nervous system through the blood stream. The molecular tools these pathogens would require to cross the meningeal layers and the bloodbrain barrier are not yet well understood. Inside the subarachnoid, bacteria replicate and cause inflammation from released toxins such as hydrogen peroxide (H2O2) . These toxins have been found to damage the mitochondria and produce a large scale immune response. Headache and meningismus are often signs of inflammation relayed via trigeminal sensory nerve fibers within the pia mater. Disabling neuropsychological effects are seen in up to half of bacterial meningitis survivors. Research into how bacteria invade and enter the meningeal layers is the next step in prevention of the progression of meningitis.[14]

A tumor growing from the meninges is referred to as a meningioma. Most meningiomas grow from the arachnoid mater inward applying pressure on the pia mater and therefore the brain or spinal cord. While meningiomas make up 20% of primary brain tumors and 12% of spinal cord tumors, 90% of these tumors are benign. Meningiomas tend to grow slowly and therefore symptoms may arise years after initial tumor formation. The symptoms often include headaches and seizures due to the force the tumor creates on sensory receptors. The treatments available for these tumors include surgery and radiation.[15]

Median sagittal section of brain

Coronal section of inferior horn of lateral ventricle

Diagrammatic representation of a section across the top of the skull, showing the membranes of the brain, etc.

Diagrammatic section of scalp

Ultrastructural diagram of the cerebral cortex (Viorel Pais, 2012)

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Pia mater - Wikipedia

Spinal Cord Stem Cells Comments Off on Pia mater – Wikipedia | January 8th, 2017

It may sound like science fiction, but the research of Stephanie Willerth of the University of Victoria is proving to be anything but. A patients adult cells will be reprogrammed back into their stem cell state.....

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Septic shock is the most severe form of infection seen in intensive care units (ICUs), a sneaky and unpredictable condition according to the Ottawa Health Research Institutes Dr. Lauralyn McIntyre...

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Its been 12 years since Canada passed legislation governing research on human embryos. As it stands, the legislation has not kept pace with the science... ...

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Umbilical cord blood can be a promising source of hematopoietic stem cells (HSCs), used in treating blood diseases...

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Liver transplants save lives, plain and simple. But they also sentence recipients to a lifetime of immune-suppressive drugs, to prevent the body from rejecting the foreign addition....

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Its an exciting time for the Stem Cell Network! We have been very busy over the past few months ensuring that we are able to deliver on our mandate and see research funding and training opportunities provided for...

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Spinal Cord Stem Cells Comments Off on Stem Cell Network | January 7th, 2017

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Neurology - Spinal Cord Introduction - YouTube

Spinal Cord Stem Cells Comments Off on Neurology – Spinal Cord Introduction – YouTube | January 6th, 2017

Clinical trials using neural stem cells

Neural stem cells (mouse)

StemCell Inc In December 2010 the Swiss regulatory agency for therapeutic products gave the go-ahead for aStemCell, Inc.-SponsoredPhase I/II clinical trial on chronic spinal cord injuryat the Balgrist University Hospital in Zurich (Switzerland). This trial had been inspired by the preclinical evidence of direct oligodendrocyte cell replacement through human neural stem cell (NSC) transplants in early chronic SCI in a particular mouse model. The trial uses a type of stem cell derived from human brain tissue and can make any of the three major kinds of neural cells found in the central nervous system. A single donor can provide eough cells for several transplanted patients). A single dose (20 x 106cells) of HuCNS-SC is directly implanted through multiple injections into thethoracicspinal cord of patients with chronic thoracic (T2T11) SCI, and immune suppression administered for 9 months after transplantation. This trial had enrolled patients 312 months after complete and incomplete cord injuries. The estimated completion date of this study is March 2016 (clinicaltrials.govidentifier no. NCT01321333). Interim analysis of clinical data to May 2014, presented at the Annual Meeting of the American Spinal Injury Association in San Antonio, Texas has shown that the significant post-transplant gains in sensory function first reported in two patients have now been observed in two additional patients.

The next group of patients currently being recruited in North America (University of Calgary) as well as in Switzerland has included some with incomplete injuries (ie some retained sensory or motor function) (clinicaltrials.govidentifier no. NCT01725880).

Earlier last year, the same company completed enrollment in multicentre open-label Phase I/II clinical titled "Study of Human Central Nervous System (CNS) Stem Cell Transplantation in Cervical Spinal Cord Injury" (Pathway Study website;clinicaltrials.govidentifier no. NCT02163876). The Pathway Study is the first clinical study designed to evaluate both the safetyandefficacy of transplanting stem cells. A total of 52 patients with traumatic injury to the cervical spinal cord are enrolled in the trial. The trial will be conducted as a randomized, controlled, single blind study and efficacy will be primarily measured by assessing motor function according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The primary efficacy outcome will focus on change in upper extremity strength as measured in the hands, arms, and shoulders. The trial will follow the patients for one year from the time of enrollment.

The hope is that when transplanted into the injured spinal cord, these cells may re-establish some of the circuitries important for the network of nerves that carry information around the body.

Neuralstem Neuralstembegan surgeries in a Phase I safety trial of its NSI-566 neural stem cells for chronic spinal cord injury (cSCI) at the University of California, San Diego School of Medicine, with support from the UC San Diego Sanford Stem Cell Clinical Center, in September 2014 (clinicaltrials.govidentifier no. NCT01772810). The FDA amended the Phase I trial protocol to include a total of four patients, as the safety of the same cells and a similar procedure were proven in Neuralstems NSI-566/ALS trials. The four cSCI patients, with thoracic spinal cord injuries (T2-T12), have an American Spinal Injury Association (AIS) grade A level of impairment one-to-two years post-injury. This means that they have no motor or sensory function in the relevant segments at or below the injury, and are considered to be completely paralysed.

All patients in the trial will receive six injections in, or around, the injury site, using the same cells and similar procedure as the companys Amyotrophic Lateral Sclerosis (ALS) trials (the first FDA-approved neural stem cell trial for the treatment of ALS). All patients will also receive physical therapy post-surgery to guide newly formed nerves to their proper connections and functionality. The patients will also receive immunosuppressive therapy, which will be for three months, as tolerated. The trial study period will end six months post-surgery of the last patient, with a one-year Phase I completion goal. An NSI-566/acute spinal cord injury Phase I/II trial is expected to commence in the first quarter of 2015 in Seoul, South Korea.

The Miami Project to Cure Paralysis The Miami Projectclinical researchers currently have several clinical trials and clinical studies available for people who have had a spinal cord injury; some are for acute injuries and some are for chronic injuries. The clinical trials are testing the safety and efficacy of different cellular, neuroprotective, reparative, or modulatory interventions. These include Phase I clinical trials with the patients own (peripheral nerve-derived) Schwann cells in bothsubacute thoracicandchronic cervical and thoracicSCIs and a multicenter Phase II clinical trial withHuCNS-SC in chronic cervical SCIs(as above). All these Miami Project cell therapy trials are recruiting patients (more info on clinicaltrials.gov).

Mesenchymal/stromal stem cellsare being investigated as possible treatments for spinal cord injuries. Clinical Trials (clinicaltrials.gov) identifies at present total of 9 trials tagged as MSC trials in spinal cord injuries. These include studies that investigate the safety and efficacy of MSCs derived from the patients own bone marrow (5), adipose tissue (fat) (3) or cord blood (1). MSCs are injected in a number of different ways in these trials - including directly into the spinal cord or the lesion itself, intravenously, or even just in the skin, in patients with chronic cervical to thoracic injuries showingASIA/ISCoS scoresbetween A (complete lack of motor and sensory function below the level of injury) and C (some muscle movement is spared below the level of injury, but 50 percent of the muscles below the level of injury cannot move against gravity).

The hope is that when transplanted into the injured spinal cord, these cells may provide tissue protective molecules/factors and help (indirectly from cell integration and differentiation) to re-establish some of the circuitries important for the network of nerves that carry information around the body.

California based biotech Geronhad a widely reported clinical trial under way for a treatment the first of its kind involving the injection of cells derived from human embryonic stem cells. The injected cells were precursors of oligodendrocytes, the cells that form the insulating myelin sheath around axons. Researchers hoped that these cells, once injected into the spinal cord, would mature and form a new coating on the nerve cells, restoring the ability of signals to cross the spinal cord injury site.

After treating four patients with these cells in a phase one (safety) trial, and reporting no serious adverse effects, Geron announced in November 2011 it was discontinuing its stem cell programme. The company said stem cells continue to hold great promise, but cited financial reasons for shifting focus to other areas of research.

Asterias Biotherapeutics Following up on the cellular technology initially developed by Geron, Asterias Biotherapeutics has developed a program that focuses on the development of a kind of nerve cell, oligodendrocyte progenitor cells (OPCs) for spinal cord injury. These cells, known as AST-OPC1, are produced from human embryonic stem (ES) cells.

In aPhase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million hES cell-derived OPCs at the spinal cord injury site 7-14 days post-injury. The subjects received low levels immunosuppression for the next 60 days. Delivery of OPCs was successful in all five subjects with no serious adverse events associated with the administration of the cells or the immunosuppressive regimen. In four of the five subjects, serial MRI scans suggested reduction of the volume of injury in the spinal cord

A second follow up (dose escalation)Phase I/II trialwith AST-OPC1 in acute (14-30 days after injury) sensorimotor complete cervical spinal cord injuries (SCI) is currently recruiting participants.

The hope is that when acutely transplanted into the injured spinal cord, OPCs may remyelinate and restore lost functions.

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December 13, 2016 - Experimental implant shows promise for restoring voluntary movement after spinal cord injury

UCLA scientists test electrical stimulation that bypasses injury; technique boosts patients finger control, grip strength up to 300 percent A spinal stimulator being tested by doctors at Ronald Reagan UCLA Medical Center is showing promise in restoring hand strength and movement to a California man who broke his neck in a dirt bike accident five Continue Reading

Researchers have developed a urine test revealing the presence of a neurotoxin that likely worsens the severity and pain of spinal cord injuries, suggesting a new tool to treat the injuries. The neurotoxin, called acrolein, is produced within the body after nerve cells are damaged, increasing pain and triggering a cascade of biochemical events thought Continue Reading

We are trying to improve someones quality of life. If someone can breathe without a ventilator, then youve increased their independence, and that, to me, is a huge success. Michael Lane, PhD Walking is not the top priority for many patients who have suffered from cervical spinal cord injuries, according to Michael Lane, PhD, an Continue Reading

Scientists have developed a robotic interface which could help to restore fine hand movements in paraplegics. By combining an electrode cap with an exoskeleton worn over the fingers, the device translates brain signals to hand movements. The approach could provide paraplegic patients with the fine motor control needed to carry out everyday tasks such as Continue Reading

In the course of three years, Taylor Graham has accomplished many things: Survived a motorcycle accident, adjusted to a spinal cord injury and a new life in a wheelchair, picked up the sport of wheelchair tennis, graduated from Southeast Community College, and even got married. So what could possibly be next? We have a goal Continue Reading

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Spinal Cord Injury Zone!

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Spinal cord injuries result from damage to the vertebrae, ligaments or disks of the spinal column or to the spinal cord itself.

A traumatic spinal cord injury may stem from a sudden, traumatic blow to your spine that fractures, dislocates, crushes, or compresses one or more of your vertebrae. It also may result from a gunshot or knife wound that penetrates and cuts your spinal cord.

Additional damage usually occurs over days or weeks because of bleeding, swelling, inflammation and fluid accumulation in and around your spinal cord.

A nontraumatic spinal cord injury may be caused by arthritis, cancer, inflammation, infections or disk degeneration of the spine.

The central nervous system comprises the brain and spinal cord. The spinal cord, made of soft tissue and surrounded by bones (vertebrae), extends downward from the base of your brain and is made up of nerve cells and groups of nerves called tracts, which go to different parts of your body.

The lower end of your spinal cord stops a little above your waist in the region called the conus medullaris. Below this region is a group of nerve roots called the cauda equina.

Tracts in your spinal cord carry messages between the brain and the rest of the body. Motor tracts carry signals from the brain to control muscle movement. Sensory tracts carry signals from body parts to the brain relating to heat, cold, pressure, pain and the position of your limbs.

Whether the cause is traumatic or nontraumatic, the damage affects the nerve fibers passing through the injured area and may impair part or all of your corresponding muscles and nerves below the injury site.

A chest (thoracic) or lower back (lumbar) injury can affect your torso, legs, bowel and bladder control, and sexual function. In addition, a neck (cervical) injury affects movements of your arms and, possibly, your ability to breathe.

The most common causes of spinal cord injuries in the United States are:

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The spine has different sections. The level of paralysis depends on the location of the injury.The spinal cord is made up of millions of nerve cells that send projections up and down the cord and out into other parts of the body. The information that allows us to sit, run, go to the toilet and breathe travels along these projections, called nerves.

When the spinal cord is injured, the initial trauma causes cell damage and destruction, and triggersa cascade of eventsthat spread around the injury site affecting a number of different types of cells. Axons are crushed and torn, and oligodendrocytes, the nerve cells that make up the insulating myelin sheath around axons, begin to die. Exposed axons degenerate, the connection between neurons is disrupted and the flow of information between the brain and the spinal cord is blocked.

The body cannot replace cells lost when the spinal cord is injured, and its function becomes impaired permanently. Patients may end up with severe movement and sensation disabilities. They will generally be paralyzed and without sensation from the level of the injury downwards.

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