Dec. 19, 1997 Findings, published in Nature, challenge long-held beliefs on adult nerve regeneration
CLEVELAND - Neuroscientists from the Case Western Reserve University School of Medicine have shown that transplanted adult nerve cells can regenerate their axons in the adult rat brain's nerve fiber pathways, challenging long-held beliefs that this is impossible.
In their study, researchers found that nerve cells regenerated remarkably well and at relatively high rates of speed in 34 of 41 animals. Their paper is published in the December 18-25 issue of the journal Nature.
It is widely accepted that the adult mammalian central nervous system will not permit regeneration of nerve cell processes, called axons. In addition to physical or molecular barriers presented by scarring at a lesion site (such as a spinal cord injury), normal adult nerve pathways, which are insulated with white matter called the myelin sheath, are thought to be impenetrable to nerve regeneration. A 10-year old theory holds that the myelin sheath contains a type of cell which prohibits nerve regeneration.
Lead author Stephen J. A. Davies, a CWRU research associate, and colleagues removed dorsal root ganglion neurons from adult donor animals and then used a unique microtransplantation system to transplant them into the brain's nerve pathways of other adult animals. They witnessed rapid growth (1 millimeter per day) and saw that 80 percent of the cells were able to extend axon processes all the way into the brain's gray matter where they branched off in new directions, acting like normal nerve cells.
"These results were totally unexpected. There is a huge potential for regeneration in the adult white matter tracks of the central nervous system, at least with the nerve cells that we've used so far," said Jerry Silver, Ph.D., professor of neurosciences at CWRU and senior author of the study. "There's not a minimal potential. It's enormous."
The scientists believe that their method of transplantation played a key role in their results. Davies, a research associate in Silver's lab, developed the method, which introduces the nerve cells with little or no trauma to them or the host brain. The minimization of scarring may be important because the researchers found scar tissue around the transplanted cells in the study's seven animals that did not regenerate nerve cells. Within the scar tissue, they found a type of inhibitory molecule called chondroitin sulphate proteoglycan.
"In the failed transplants," said Davies, "every single regrowing axon had either stopped within the proteoglycan rich boundary or had actively turned away from the boundary and looped back into the transplant interior."
Silver said, "It gives great hope that regeneration might be possible, if we can learn how to breach the immediate vicinity of the lesion by building a bridge across that zone or breaking down the inhibitory scar molecules, we may get regeneration beyond what we ever dreamed possible."
Other authors on the study are M.T. Fitch, S.P. Memberg, and A.K. Hall of the Department of Neurosciences at CWRU's School of Medicine; and G. Raisman of the Norma and Sadi Lee Research Centre in the National Institute for Medical Research's Division of Neurobiology in London. Davies is also affiliated with this research center.
The research is funded by the International Spinal Research Trust, David Heumann Fund, Brumagin Memorial Fund, and the National Institutes of Health.
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