Injury to axons, such as in the spinal cord or the central nervous system in generate initiates a cascade of complex events, the net effect of which is a functionally limiting neurological deficit. The magnitude of the deficit is determined not only by the extent of the initial injury but also, by variation within the inflammatory, degenerative and attempted regenerative events that follow the initial injury. In order to devise strategies that can improve the likelihood of a more favorable neurological outcome,.we must first understand the fundamental cellular mechanisms influence degenerative and regenerative events within the CNS. One potential mechanism that may improve the potential for axon regeneration is the presence of a favorable substrate. Recent reports suggest the hypothesis that specific subpopulations of glial cells, in particular the ensheathing cells of the olfactory nerve, may provide an optimal substrate. The ultimate goal of the projects described in this program is to test the hypothesis that transplants of specific glial suspensions can promote recovery in the injured spinal cord. This proposal seeks to develop a body of knowledge that will help us to identify basic mechanisms that influence regenerations in axons following injury. Building on that knowledge, we hope to identify specific mechanisms that may be susceptible to intervention strategies that would improve outcome following spinal cord injury. The program is divided into 3 major areas: 1) A Core facility providing support for electron microscopy and administration; 2) Studies designed to test specific hypotheses about the mechanisms underlying axonal responses to injury and growth properties and the degree to which these can be modified by different glial substrates; and 3) Studies on the degree to which injury-induced demyelination and axon transection can be overcome in the spinal cord with cell transplants. Pursuing these studies will fill critical gaps in our current understanding of degenerative/regenerative processes occurring within the central nervous system. This knowledge is essential for the development of treatment strategies directed not only at the spinal cord, but the central nervous system in general.
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