FACTORS AFFECTING REGENERATION THROUGH THE GLIAL SCAR

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The population of cells in the glial scar induced by a penetrating injury of the adult rat central nervous system is high in neuronotrophic and neurite promoting activity but is unable to augment neuronal survival or promote axonal regeneration - Why? To address this question, I will determine 1) which subset of cells in the glial scar possesses neuronotrophic factors and expresses neurite promoting activity, 2) whether the level of these factors changes with age, 3) whether the neurite promoting factors in the glial scar are masked so that axons are unable to 'see' them and 4) whether neuronotrophic factor activity although present is inhibited by other components in the glial scar. My model for examining these questions will be the intra-parenchymal nitrocellulose implant developed by Silver et al. (1982) in which a nitrocellulose filter placed into the brain of a critical period animal (younger than 8 day of age) is soon invaded by nearby astrocytes and incorporated into the brain. Such cell coated implants promote axonal growth across their surface. Implantation in post-critical period brain (greater than 8 days of age) results in the formation of a glial scar on the filter consisting of astrocytes, fibroblasts, macrophages and laminin containing basal lamina - a surface which is refractory to axonal growth. By removing the implants from critical or post critical period animals I have found that it is possible to place them intact into serum-free culture for several days and maintain their cell viability. This results in a mixed population of functionally defined cells which can be manipulated in culture to answer the above questions. Any positive results obtained from cell culture studies can be immediately examined in vivo by either reintroducing the modified implant into an audit animal or inhibiting components of the scar which make it refractory.