| Abstract No.: | 218 |
| Country: | Canada |
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| Title: | Early Events in Nerve Regeneration |
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| Authors/Affiliations: | Douglas Zochodne
Regeneration Unit, Hotchkiss Brain Institute, University of Calgary, AB, Canada
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| Content: | Peripheral nerves are the essential connections between the brain, spinal cord and the body. Impaired peripheral nerve regeneration leads to paralysis, sensory loss and intractable neuropathic pain. The success of nerve regeneration depends on a series of early and later events, both at the level of the perikaryon (cell body) and the local microenvironment that new axons traverse. The present talk will emphasize aspects of the early outgrowth of axons from peripheral nerve trunk injury sites. Important highlights of early regrowth include the formation of axonal endbulbs and their accumulation of functional molecules and enzymes capable of influencing the regenerative milieu. Early axonal sprouting is at first independent of perikaryal support but later depends on a supply of structural and other proteins. Local axon and growth cone protein synthesis may be critical to early axon behaviour. CGRP (calcitonin gene-related peptide), for example, is upregulated in outgrowing axon sprouts through local synthesis and once released acts on receptors expressed by local Schwann cells (SCs) to induce proliferation. SC proliferation and outward migration are then essential for the success of regeneration. There is an intense molecular exchange between axons and SCs that involves not only CGRP but more widely reported neuregulins, laminin and growth factors. Axons and SCs make guidance decisions together that can be misdirected after severe transection injuries. Upregulated proteoglycans and probably semaphorins after both crush and transection inhibit outgrowth through the RHOA GTPase signalling pathway. RGD signalling moieties of fibronectin signal axon integrin receptors to facilitate outgrowth. Finally, the success of early outgrowth is critically dependent on the speed and success of Wallerian and Wallerian-like degeneration in clearing myelin and axon debris to permit new ingrowth.
[Supported by CIHR, CDA and AHFMR]
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