Posts tagged spinal cord injury
Articles and news from the latest research reports.
Reflex control could improve walking after incomplete spinal injuries
A training regimen to adjust the body’s motor reflexes may help improve mobility for some people with incomplete spinal cord injuries, according to a study supported by the National Institutes of Health.
During training, the participants were instructed to suppress a knee jerk-like reflex elicited by a small shock to the leg. Those who were able to calm hyperactive reflexes – a common effect of spinal cord injuries – saw improvements in their walking.
The study was led by Aiko Thompson, Ph.D., and Jonathan Wolpaw, M.D., both of whom hold appointments at the New York state Department of Health and the State University of New York in Albany, and at Columbia University in New York City. The study took place at Helen Hayes Hospital in West Haverstraw, N. Y. It was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), and published in the Journal of Neuroscience.
"People tend to think of reflexes as fixed, but in reality, normal movement requires constant fine tuning of reflexes by the brain. Loss of that fine-tuning is an important part of the disability that comes with a spinal cord injury," said Dr. Wolpaw, a research physician and professor at the Wadsworth Center, the state health department’s public health laboratory.
When the brain makes a decision to move, it sends signals that travel through the spinal cord to the appropriate muscles. Spinal reflexes – controlled by local circuits of nerve cells in the spinal cord – provide a way for the body to react and move quickly without a conscious decision from the brain. “They enable you to jerk your hand away from a hot stove before you’ve registered the pain and experienced severe burns,” Dr. Wolpaw said. “The brain can gradually enhance or suppress reflexes as needed,” he said.
First Oral Drug for Spinal Cord Injury Improves Movement in Mice
An experimental oral drug given to mice after a spinal cord injury was effective at improving limb movement after the injury, a new study shows.
The compound efficiently crossed the blood-brain barrier, did not increase pain and showed no toxic effects to the animals.
“This is a first to have a drug that can be taken orally to produce functional improvement with no toxicity in a rodent model,” said Sung Ok Yoon, associate professor of molecular & cellular biochemistry at Ohio State University and lead author of the study. “So far, in the spinal cord injury field with rodent models, effective treatments have included more than one therapy, often involving invasive means. Here, with a single agent, we were able to obtain functional improvement.”
The small molecule in this study was tested for its ability to prevent the death of cells called oligodendrocytes. These cells surround and protect axons, long projections of a nerve cell, by wrapping them in myelin. In addition to functioning as axon insulation, myelin allows for the rapid transmission of signals between nerve cells.
The drug preserved oligodendrocytes by inhibiting the activation of a protein called p75. Yoon’s lab previously discovered that p75 is linked to the death of these specialized cells after a spinal cord injury. When they die, axons that are supported by them degenerate.
“Because we know that oligodendrocytes continue to die for a long period of time after an injury, we took the approach that if we could put a brake on that cell death, we could prevent continued degeneration of axons,” she said. “Many researchers in the field are focusing on regeneration of neurons, but we specifically targeted a different type of cells because it allows a relatively long therapeutic window.”
An additional benefit of targeting oligodendrocytes is that it can amplify the therapeutic effect because a single oligodendrocyte myelinates multiple axons.
A current acute treatment for humans, methylprednisolone, must be administered within eight but not more than 24 hours after the injury to be effective at all. An estimated 1.3 million people in the United States are living with spinal cord injuries, experiencing paralysis and complications that include bladder, bowel and sexual dysfunction and chronic pain.
The experimental drug, called LM11A-31, was developed by study co-author Frank Longo, professor of neurology and neurological sciences at Stanford University. The drug is the first to be developed with a specific target, p75, as a potential therapy for spinal cord injury.
The research is published in the Jan. 9, 2013, issue of The Journal of Neuroscience.
Researchers gave three different oral doses of LM11A-31, as well as a placebo, to different groups of mice beginning four hours after injury and then twice daily for a 42-day experimental period. The scientists analyzed the compound’s effectiveness at improving limb movement and preventing myelin loss.
The spinal cord injuries in mice mimicked those caused in humans by the application of extensive force and pressure, resulting in loss of hind-limb and bladder function andexperimentally calibrated baseline difficulty in walking and swimming.
The researchers determined that the mice did not experience more pain than the placebo group at all the doses tested, suggesting that LM11A-31 does not worsen nerve pain after spinal cord injury.
Analysis showed that the extent of myelin sparing was dependent on the dose of the drug. Each dose – 10, 25 or 100 milligrams per kilogram of body weight – led to increasing myelin sparing, with the highest dose demonstrating the greatest effect.
The injury in the animals caused a loss of about 75 percent of myelinated axons in the lesion area in the placebo group. This loss was reduced so that myelinated axons reached more than half of the normal levels with LM11A-31 at 100 mg/kg. That was correlated with about a 50 percent increase in surviving oligodendrotcytes compared to those in the placebo group, Yoon said.
In behavior tests, only the highest dose of the compound led to improvements in motor function. Mice were tested in both weight-bearing and non-weight-bearing activities over the 42 days to evaluate their functional recovery.
Mice receiving the highest dose could walk with well-coordinated steps. In swimming tests, scientists saw similar improvements, with mice receiving the highest dose most able to coordinate hind-limb crisscross movement. The other treatment groups exhibited difficulty in walking and swimming.
Yoon said the findings may suggest that myelin sparing needs to reach a threshold of roughly 50 percent of normal levels before motor function improvements become measurable.
“The cellular analysis of the myelin profile detects small changes. Behavior is more complex, and we don’t think functional behavior necessarily improves in a linear fashion,” she said. “Still, these results clearly show that this is the first oral drug in spinal cord injury that works alone to improve function.”
(Source: researchnews.osu.edu)
Hybrid tunnel may help guide severed nerves back to health
Building a tunnel made up of both hard and soft materials to guide the reconnection of severed nerve endings may be the first step toward helping patients who have suffered extensive nerve trauma regain feeling and movement, according to a team of biomedical engineers.
"Nerve injury in both central nervous system and peripheral nervous system is a major health problem," said Mohammad Reza Abidian, assistant professor of biomedical engineering, Penn State. "According to the National Spinal Cord Injury Statistical Center, there are approximately 290,000 individuals in the US who suffer from spinal cord injuries with about 12,000 new injuries occurring each year."
Spontaneous nerve regeneration is limited to small lesions within the injured peripheral nerve system and is actively suppressed within central nervous system. When a nerve in the peripheral nervous system is cut slightly, nerve endings can regenerate and reconnect. However, if the distance between the two endings is too far, the growth can go off course and fail to connect.
The researchers, who published their results in the current issue of Advanced Healthcare Materials, developed a novel hybrid conduit that consisted of a soft material, called a hydrogel, as an external wall along with an internal wall made of an electrically-active conducting polymer to serve as a tunnel that guides the regrowth and reconnection of the severed nerve endings.
Abidian said that the method could offer advantages over current surgeries that are used to reconnect severed nerves.
"Autografts are currently the gold standard for bridging nerve gaps," said Abidian. "This is an operation that takes the nerve from another portion of the body — for instance — from a tendon, and then it is grafted onto the injured nerve."
However, the operation can be painful and there are often mismatches in size between the severed nerve endings and the new grafted portion of the nerve, Abidian said.
Exoskeleton suit gives man chance to walk again
Cutting edge technology has a Darien man taking miraculous steps.
He was paralyzed after he was struck by a car while riding his bike, training for an ironman four years ago.
Mike Loura was beaming as he was walking and showcasing this amazing robotic exoskeleton technology. He was doing something he never imagined he’d be able to do again.
"Ever since the accident all the doctors said you’re never going to walk again," Loura said.
However, the husband and father of two girls is walking again. Thursday was day 15, the day Loura strapped on the wearable robot, a breakthrough technology, but it’s the first time he’s taking steps for others to see.
"Every time I take a step I kinda have to balance myself in a certain position for the machine to know that it’s ready to take the next step," said Loura.
"It has an exoskeleton system with battery powered motor that allows someone who can’t feel and can’t move," said Dr. David Rosenblum, "who’s paralyzed, the ability to go from sit to stand to actually taking steps."
Dr. Rosenblum is the medical director of Rehabilitation at Gaylord Specialty Healthcare, the only center in Connecticut to offer the Ekso Bionics’ Robotic Exoskeleton technology to patients with spinal chord injuries.
"We’re using it as a tool to work on balance to get someone up and moving," said Dr. Rosenblum. "From a wellness perspective to improve their quality of life."
Scientists Identify Two Genes Essential for Breathing
A team of researchers at the New York University’s Langone Medical Center has discovered that two genes, called Hoxa5 and Hoxc5, play a critical role in establishing the neuronal circuits required for breathing. The discovery could help advance treatments for spinal cord injuries and neurodegenerative diseases.
The three-year study published in the journal Nature Neuroscience identifies a molecular code that distinguishes a group of muscle-controlling nerve cells collectively known as the phrenic motor column (PMC).
“These cells lie about halfway up the back of the neck, just above the fourth cervical vertebra, and are probably the most important motor neurons in your body,” explained senior author Prof Jeremy Dasen of the Howard Hughes Medical Institute.
Harming the part of the spinal cord where the PMC resides can instantly shut down breathing. But relatively little is known about what distinguishes PMC neurons from neighboring neurons, and how PMC neurons develop and wire themselves to the diaphragm in the fetus. The PMC cells relay a constant flow of electrochemical signals down their bundled axons and onto the diaphragm muscles, allowing the lungs to expand and relax in the natural rhythm of breathing.
“We now have a set of molecular markers that distinguish those cells from other populations of motor neurons, so that we can study them in detail and look for ways to selectively enhance their survival,” Prof Dasen said.
Discovery may help nerve regeneration in spinal injury
Scientists at the Universities of Liverpool and Glasgow have uncovered a possible new method of enhancing nerve repair in the treatment of spinal cord injuries.
It is known that scar tissue, which forms following spinal cord injury, creates an impenetrable barrier to nerve regeneration, leading to the irreversible paralysis associated with spinal injuries. Scientists at Liverpool and Glasgow have discovered that long-chain sugars, called heparan sulfates, play a significant role in the process of scar formation in cell models in the laboratory.
Research findings have the potential to contribute to new strategies for manipulating the scarring process induced in spinal cord injury and improving the effectiveness of cell transplantation therapies in patients with this type of injury.
Scarring occurs due to the activation, change in shape, and stiffness of cells, called astrocytes, which are the major nerve support cells in the spinal cord. One possible way to repair nerve damage is transplantation of support cells from peripheral nerves, called Schwann cells. The team, however, found that these cells secrete heparan sulfate sugars, which promote scarring reactions and could reduce the effectiveness of nerve repair.
Scientists showed that these sugars can over-activate protein growth factors that promote astrocyte scarring. Significantly, however, they found this over-activation could be inhibited by chemically modified heparins made in the laboratory. These compounds could prevent the scarring reaction of astrocyte cells, opening up new opportunities for treatment of damaged nerve cells.
Professor Jerry Turnbull, from the University of Liverpool’s Institute of Integrative Biology, said: “Spinal injury is a devastating condition and can result in paralysis for life. The sugars we are investigating are produced by nearly every cell in the body, and are similar to the blood thinning drug heparin.
"We found that some sugar types promote scarring reaction, but remarkably other types, which can be chemically produced in the laboratory by modifying heparin, can prevent this in our cell models.
"Studies in animal cells are now needed, but the exciting thing about this work is that it could, in the future, provide a way of developing treatments for improving nerve repair in patients, using the body’s own Schwann cells, supplemented with specific sugars."
Professor Sue Barnett, from the University of Glasgow’s Institute of Infection, Immunity and Inflammation, said: “We had already shown that Schwann cells, identified as having the potential to promote nerve regrowth, induced scarring in spinal cord injury. Now that we know that they secrete these complex sugars, which lead to scarring, we have the opportunity to intervene in this process, and promote central nervous system repair.”
(Source: eurekalert.org)
Researchers identify gene required for nerve regeneration
A gene that is associated with regeneration of injured nerve cells has been identified by scientists at Penn State and Duke University. The team, led by Melissa Rolls, an assistant professor of biochemistry and molecular biology at Penn State, has found that a mutation in a single gene can entirely shut down the process by which axons — the parts of the nerve cell that are responsible for sending signals to other cells — regrow themselves after being cut or damaged. “We are hopeful that this discovery will open the door to new research related to spinal-cord and other neurological disorders in humans,” Rolls said. The journal Cell Reports published an early online copy of the paper (Nov. 1), and also will include the paper in the monthly issue of the journal, which will be published Nov. 29.
Advanced exoskeleton promises more independence for people with paraplegia
The dream of regaining the ability to stand up and walk has come closer to reality for people paralyzed below the waist who thought they would never take another step.
A team of engineers at Vanderbilt University’s Center for Intelligent Mechatronics has developed a powered exoskeleton that enables people with severe spinal cord injuries to stand, walk, sit and climb stairs. Its light weight, compact size and modular design promise to provide users with an unprecedented degree of independence.
The university has several patents pending on the design and Parker Hannifin Corporation – a global leader in motion and control technologies – has signed an exclusive licensing agreement to develop a commercial version of the device, which it plans on introducing in 2014.
Paralysis breakthrough: spinal cord damage repaired
I suddenly noticed I could move my pinkie. I was cruising towards the highway when this old guy tried to cross the 4-lane road really fast. He hit me and I ejected over to the opposite lane. Luckily someone found me before the traffic got to me.
Paralysis may no longer mean life in a wheelchair. A man who is paralysed from the trunk down has recovered the ability to stand and move his legs unaided thanks to training with an electrical implant.
Andrew Meas of Louisville, Kentucky, says it has changed his life. The stimulus provided by the implant is thought to have either strengthened persistent “silent” connections across his damaged spinal cord or even created new ones, allowing him to move even when the implant is switched off.
The results are potentially revolutionary, as they indicate that the spinal cord is able to recover its function years after becoming damaged.
Previous studies in animals with lower limb paralysis have shown that continuous electrical stimulation of the spinal cord below the area of damage allows an animal to stand and perform locomotion-like movements. That’s because the stimulation allows information about proprioception – the perception of body position and muscle effort – to be received from the lower limbs by the spinal cord. The spinal cord, in turn, allows lower limb muscles to react and support the body without any information being received from the brain (Journal of Neuroscience, doi.org/czq67d).
Last year, Susan Harkema and Claudia Angeli at the Frazier Rehab Institute and University of Louisville in Kentucky and colleagues tested what had been learned on animals in a man who was paralysed after being hit by a car in 2006. He was diagnosed with a “motor complete” spinal lesion in his neck, which means that no motor activity can be recorded below the lesion.
Mr. Abicca, a 17-year-old from San Diego, is essentially wearing a robot. His bionic suit consists of a pair of mechanical braces wrapped around his legs and electric muscles that do much of the work of walking. It is controlled by a computer on his back and a pair of crutches held in his arms that look like futuristic ski poles.
Since an accident involving earth-moving equipment three years ago that damaged his spinal cord, Mr. Abicca has been unable to walk on his own. The suit, made by a company called Ekso Bionics, is an effort to change that.