Cut Nerve Fibers Are Repaired In An Animal Model Of Spinal Cord Injury; May Help Repair Nerve Damage In Humans

"The technique rejoins the cut or crushed ends of severed central and peripheral nerve cells so that the repaired cells again conduct electrical signals through the severed area within seconds to minutes after they are rejoined," says George Bittner, Ph.D., of the University of Texas at Austin. The central nervous system (CNS) includes the brain and spinal cord; the peripheral nervous system (PNS) includes nerves found in the rest of the body.

Several hundred thousand central and peripheral nervous system injuries occur annually in the United States, primarily due to trauma and stroke. There is currently no technique in humans or other mammals which can repair severed nerves in the brain or spinal cord or speed up the repair of severed peripheral nerves.

"The technique opens up a completely novel approach to restoring physiological continuity in the injured nervous system," says Michael Selzer, M.D., Ph.D., a neurologist at the University of Pennsylvania.

Bittner's study, funded in part by the National Institutes of Health, is published in the April 1 issue of The Journal of Neuroscience.

Nerve cells possess axons, extensions that transmit electrical signals over long distances in the body. When these biological transmission lines are cut, their electrical signals can no longer be transmitted. Nerve cells in mammals, including humans, usually cannot regenerate axons that are severed in the CNS. At present, the functions once controlled by those axons cannot be restored. Severed PNS axons regenerate very slowly, about one millimeter or 1/25th of an inch per day.

In the new study, Bittner and his colleagues applied a calcium-free solution of polyethylene glycol (PEG) for one to two minutes to the cut ends of severed axons. PEG causes the cell membranes of closely approximated cells to fuse. The researchers then washed off the PEG solution and bathed the site where the axons had been joined in calcium solutions that mimic the salt composition of mammalian body fluids. They found that within two to 30 minutes many of the once-severed axons regained their ability to transmit electrical impulses through the lesion site. They then applied a biological adhesive (a PEG-hydrogel) developed by one of the authors, Jeffery Hubbell, Ph.D., who is now at the Swiss Federal Institute in Zurich, Switzerland. This substance binds very tightly to the severed axons and prevents the rejoined axons from pulling apart once the animal recovers from anesthesia.

The researchers have now successfully used this technique to rejoin the severed halves of CNS and PNS axons from crayfish, earthworms, rats, rabbits, and guinea pigs. "This new approach can almost certainly be used to rapidly rejoin cut or crushed axons in humans," Bittner says. To aid this effort, Bittner and his colleagues have already published papers showing how the severed ends of mammalian axons can be kept alive for at least days after they are disconnected from their parent cells. An ability to keep severed axons alive would give surgeons a longer time to rejoin those axons with PEG solutions.

Selzer emphasizes that, until now, demonstrations that fused mammalian nerve fibers can conduct electrical impulses have been performed in tissue isolated from the body. Among crucial questions that remain are whether the technique can fuse axons in a living mammal and whether this approach can result in recovery of useful function.

Bittner's co-authors also included April Lore, David Bobb, Martis Ballinger, Keisha Loftin, Jeffory Smith, Mark Smyers and Hubacuc Garcia. Bittner is a member of the Society for Neuroscience, an organization of more than 28,000 basic scientists and clinicians who study the brain and nervous system. The Society publishes The Journal of Neuroscience.