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May 24, 2013
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New Nerve Circuits


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National Spinal Cord Injury Association

Foundation for Spinal Cord Injury Prevention, Care & Cure

Spinal Cord Injury Resource Center



   10.28.04
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Friends and family will gather to pay tribute to Christopher Reeve on Friday in New York City. His activism helped to draw attention to the importance of spinal cord injury research. Now, an international group of scientists has succeeded in growing new circuits of nerves after injury that they hope may someday help paraplegics like Reeve walk again.

Growing New Hope

Christopher Reeve, best known for his role as Superman, remained in the limelight in recent years as an advocate of increased funding and research for spinal cord injuries and other central nervous system disorders. Left paralyzed from the neck down by a fall from his horse in 1995, Reeve focused his efforts through the Christopher Reeve Paralysis Foundation. He was one of an estimated 250,000 people in the U.S. living with spinal cord injuries.

Martin Schwab, a neuroscientist at The Brain Research Institute at the University of Zurich, Switzerland, and an international team of researchers have spent much of the last twenty years studying why the nerve fibers of the spinal cord and the brain don't re-grow or regenerate themselves after injury in the same way as other tissues of the body. "If you destroy a large part of the muscle tissue in a muscle, or of your liver, this tissue can re-generate," Schwab explains. "This is what is not occurring in the central nervous system."





Martin Schwab
Dr. Martin Schwab
During early childhood development, the nervous system, which consists of around 10 billion nerve cells, each one having between a thousand and ten thousand connections with other nerve cells, develops and forms an incredibly complex network. Having become stabilized, the adult central nervous system — the brain and the spinal cord — are relatively hard-wired, allowing only small changes during learning or adaptation. So when part of this system is damaged by injury or disease such as stroke, the loss of function associated with the damage is permanent. "Once you are paraplegic due to an accident which has injured your spinal cord, you remain in a wheelchair all your life," Schwab says.

Schwab discovered, as he explained recently at the 2004 meeting of The American Society for Neurochemistry in New York City, that something in the body actively prevents repair of injured nerve fibers. "One important reason why there is no repair in the brain and in the spinal cord is because repair is actually inhibited," he says. "There are blockers, inhibitors, of repair, so called neuron growth inhibitors, in particular a molecule which is called Nogo-A." Nogo-A appears to be one of the stabilizers that come into play after development of the central nervous system has finished: when all the nerve fibers have grown to their places, made their appropriate connections, and the whole network is in a functional mature state.




rat
Rats regain function after spinal cord injury
image: Martin Schwab, University of Zurich, Switzerland
Studying the affect of Nogo-A in rodents, Schwab was able to disable or neutralize the stabilizing action of this factor with a very specific antibody, an immune system protein, and allow the nerves to re-grow. "This inhibitor tells the nerve fiber which has been injured not to re-grow, and when you sort of cover it up with an antibody, the nerve cell doesn't see the one-way signal or the red light anymore and starts to grow," Schwab explains, "and, in fact, grows to original target sites and integrates into circuits which have survived the lesion of the spinal cord in a way which brings back function."

The research team's next goal, which they hope to reach within a couple of months, is to begin clinical experiments with paraplegics using antibodies against Nogo-A. For now it is uncertain how long after a spinal injury this type of treatment might be effective, but Schwab's work is only one way in which the scientific world will help to keep Christopher Reeve's mission alive.

This research was published in the May, 2004 issue of the journal Molecular and Cellular Neuroscience and was funded by The University of Zurich; the Swiss Federal Institute of Technology, Zurich; Swiss National Science Foundation and The Christopher Reeve Paralysis Foundation.


 
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