FACTORS AFFECTING REGENERATION THROUGH THE GLIAL SCAR

穿透性神经胶质瘢痕中细胞的数量 成年大鼠中枢神经系统损伤程度较高 神经营养和轴突促进活性，但不能 增强神经元存活或促进轴突再生--为什么？ 为了解决这个问题，我将确定1)哪个细胞子集 在胶质细胞中，瘢痕具有神经营养因子并表达 轴突促进活性，2)这些因素的水平 随着年龄的增长而变化，3)神经突起促进因子是否在 神经胶质疤痕被遮盖，这样轴突就看不到它们了，4) 神经营养因子活性虽然存在，但 被胶质疤痕中的其他成分抑制。我的模特是 研究这些问题将是实质内的 由Silver等人开发的硝酸纤维植入物。(1982)其中一名 在关键时期将硝酸纤维滤膜放入大脑 动物(小于8日龄)很快就会被附近的动物入侵 星形胶质细胞并结合到大脑中。这种电池被涂覆 植入物促进其表面的轴突生长。 临界期后脑内植入(大于8天 年龄)导致滤器上形成神经胶质疤痕 星形胶质细胞、成纤维细胞、巨噬细胞和层粘连蛋白 基膜--对轴突生长不起作用的表面。通过 临界期或临界期后取出种植体 我发现可以把它们完好无损地放进 无血清培养数天并保持其细胞 生存能力。这导致了功能上的混合种群 定义的细胞，可以在培养中进行操作，以回答 以上问题。从细胞培养中获得的阳性结果 这项研究可以立即在体内进行检查， 将改进的植入物重新引入审计动物或 疤痕的抑制成分使其难以愈合。

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.