FACTORS AFFECTING REGENERATION THROUGHT THE GLIAL SCAR

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DESCRIPTION: (Verbatim from the Applicant's Abstract) The dorsal column white matter tracts of the adult rat spinal cord have been tested in a novel way to learn whether the purportedly inhibitory glial scar or myelin can promote or hinder axonal regeneration of adult DRG's. This has been done by utilizing a microtransplantation technique which can introduce a small bolus of DRG cell bodies into either the unlesioned or prelesioned dorsal column white matter distal to the site of injury. This procedure allows for introduction of axotomized neurons without causing further inflammation and glial scarring at the site of implantation. The exciting results show that both normal as well as lesioned white matter away from an area of trauma are robustly permissive for long distance axon regrowth, at least for adult sensory axons. However, upon reaching the area of the forming scar, the rapidly regenerating growth cones halt abruptly and become dystrophic within a field of reactive glial matrix. It is suggested that these observations constitute compelling evidence that the glial scar and, hence, inhibitory factors such as proteoglycans at his locale, constitute the major environmental impediment to regeneration in the adult CNS. We propose to utilize the microtransplantation technique in a variety of interesting permutations of the preliminary experiments in order to explore the following questions. (1) Does a critical period exist for regeneration of adult DRG's into pre-degenerated dorsal column white matter? (2) What is the extent of reinnervation of the dorsal column nuclei or the dorsal horn grey matter by microtransplanted DRG's with increasing time after tract injury? (3) Can we develop a combinational strategy for stimulating dystrophic, transplanted DRG axons trapped within a scar, to regenerate through and beyond the glial scar? The long term goals of these experiments are to understand the basic biology that underlies the mechanisms of axon regrowth or its failure within adult white matter and to develop effective bridging strategies that allow adult axons to utilize the massive potential for regeneration which we now know exists beyond the glial scar.