| Abstract No.: | 216 |
| Country: | Canada |
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| Title: | AXON REGENERATION IN THE PERIPHERAL NERVOUS SYSTEM: LIMITATIONS AND POTENTIAL TO ACCELERATE REGENERATION |
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| Authors/Affiliations: | Tessa Gordon,
Division of Physical Medicine and Rehabilitation Medicine and Division of Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada |
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| Content: | The capacity of injured nerves to regenerate in the peripheral nervous system is frequently contrasted with the inability of injured nerves to regenerate in the central nervous system. Yet it is clinically recognized that recovery of function after peripheral nerve injuries is frequently poor. We have systematically explored the basis for this failure of recovery. We know that the slow regeneration of axons at 1-3mm/day prolongs the period in which 1) axotomized neurons remain without target connections, 2) Schwann cells are isolated from axonal contact, and 3) muscles remain denervated. Generally the failure of functional recovery has been attributed to the progressive atrophy and death of denervated muscle fibers. Our research however has shown that it is not the chronic denervation of the muscle that accounts for the failure of functional recovery. Rather, it is the first 2 factors, the chronic axotomy and the chronic denervation of Schwann cells that are the critical factors limiting functional recovery. Compounding the delays in axon regeneration is our recent findings that the outgrowth of regenerating axons across sites of lesion and surgical repair is actually much slower than was previously appreciated: periods of a month or more are required for axons to grow across a lesion site. Experiments in which we have electrically stimulated injured nerves at the time of surgical reunion of nerve stumps in both animal and human studies are demonstrating a very promising potential of brief electrical stimulation to accelerate axon outgrowth and to promote the earlier and successful reinnervation of targets. Moreover, the same 20Hz short (1h) period of electrical stimulation is also effective in accelerating outgrowth of transected sensory axons in the dorsal columns of the central nervous system. tor axons and their reinnervation of denervated targets more quickly in animals and human patients. We also demonstrate this stimulation-induced accelerated axon outgrowth for sensory axons within the lesioned central nervous system. The stimulation-induced accelerated outgrowth occurs in association with upregulation of neurotrophic factors, their receptors, elevation of cAMP and the downstream upregulation of growth-associated genes such as tubulin, GAP-43 and actin linked to axonal growth. Thus, electrical stimulation accelerates axon outgrowth which effectively translates into functional recovery. Since chronic axotomy and/or chronic denervation of Schwann cells progressively reduces regenerative capacity, it is essential to accelerate the outgrowth of axons as well as to continue to explore methods to reduce the deterioration of the growth state of the neurons and the growth supportive state of the glial cells for axon regeneration.
Operating and personal support from the CIHR and AHFMR is greatly appreciated.
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