FACTORS AFFECTING REGENERATION THROUGHT THE GLIAL SCAR

描述：(逐字摘自申请者摘要)背柱白色 成年大鼠脊髓的物质束已经以一种新的方式进行了测试 了解据称具有抑制性的胶质瘢痕或髓鞘是否能促进或 阻碍成年DRG的轴突再生。这是通过利用一种 一种可以引入一小团DRG细胞的显微移植技术 躯体进入未损毁或预损毁的背柱白质 在受伤部位的远侧。此程序允许引入 未引起进一步炎症和神经胶质瘢痕形成的轴突切断神经元 植入部位。令人兴奋的结果表明，无论是正常的还是 远离创伤区域的受损脑白质对 长距离轴突再生，至少对成年感觉神经轴突是这样。然而，一旦 到达形成疤痕的区域，快速再生的生长锥体 突然停止，并在反应性胶质基质的场内营养不良。它 认为这些观察结果构成了令人信服的证据 胶质疤痕，因此，抑制因子，如蛋白多糖在他的现场， 构成成年中枢神经系统再生的主要环境障碍。 我们建议将微移植技术应用于各种 有趣的排列的初步实验，以探索 以下是问题。(1)成体再生是否存在临界期 背根神经节进入预变性背柱白质？(2)程度有多大 背柱核团或背角灰质的再神经支配 脊髓损伤后显微移植背根神经节的时间延长？(3)我们能 开发一种刺激营养不良的移植背根神经节的组合策略 被困在疤痕中的轴突，通过胶质疤痕再生并超越胶质疤痕？ 这些实验的长期目标是了解基础生物学 这是成年后轴突再生或丧失的机制的基础。 并开发有效的桥接策略，使成年人 轴突利用我们现在知道的巨大的再生潜力 存在于神经胶质疤痕之外。

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.