FACTORS AFFECTING REGENERATION THROUGH THE GLIAL SCAR

影响胶质疤痕再生的因素

• 批准号: 3411087
• 负责人: JERRY SILVER
• 金额: $ 8.35万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411087
• 关键词: astrocytes; axon; bioassay; cell age; cytolysis; fibroblasts; glia; histology; implant; laboratory rat; laminin; macrophage; nervous system regeneration; neurons; neurotrophic factors; scars; tissue /cell culture

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.

穿透性诱导的神经胶质疤痕中的细胞群 成年大鼠中枢神经系统的伤害很高 神经营养和神经突的促进活性，但无法 增强神经元存活或促进轴突再生 - 为什么？ 要解决这个问题，我将确定1）单元格的哪个子集 在神经胶质中，疤痕具有神经营养因子并表达 神经突促进活动，2）这些因素的水平是否 随着年龄的变化，3）神经突在 神经胶质疤痕被掩盖，因此轴突无法“看到”它们和4） 虽然存在的神经营养因子活性是否是 被神经胶质疤痕中的其他组件抑制。 我的模型 检查这些问题将是范围内的 Silver等人开发的硝酸纤维素植入物。 （1982）其中 硝酸纤维素过滤器放置在关键时期的大脑中 动物（8岁以下）很快就会被附近入侵 星形胶质细胞并掺入大脑。 这样的细胞覆盖 植入物在其表面促进轴突生长。 临界后大脑中的植入（大于8天 年龄）导致在包含的过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 基底层 - 一种对轴突生长难治性的表面。 经过 从关键或关键时期中删除植入物 我发现动物可以将它们完好无损地放入 无血清培养几天并保持其细胞 生存能力。 这导致功能上的混合种群 可以在文化中操纵以回答的定义细胞 上述问题。 从细胞培养中获得的任何阳性结果 可以通过任何一个在体内检查研究 将修饰的植入物重新引入审计动物或 抑制疤痕的组成部分，使其难治性。