FACTORS AFFECTING REGENERATION THROUGH THE GLIAL SCAR

影响胶质疤痕再生的因素

• 批准号: 3411084
• 负责人: Jerry Silver
• 金额: $ 17.96万
• 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 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3411084
• 关键词: astrocytes; axon; bioassay; cell age; cytolysis; fibroblasts; glia; histology; implant; laboratory rat; laminin; macrophage; nervous system regeneration; neurons; neurotrophic factors; scars; spinal cord injury; tissue /cell culture

DESCRIPTION: (Adapted from the Applicant's Abstract.) The experiments in this proposal seek to compare and contrast the cellular and molecular mechanisms by which astroglia may inhibit the growth of axons in two regions of the spinal cord: 1) the roof plate, which is a transient boundary to dorsal column axons during development and 2) the glial dome of the dorsal root entry zone, which forms a doorway for afferents into the CNS during development but becomes a boundary to dorsal root afferent regeneration after birth. The applicant and his colleagues plan to correlate the development of the dorsal columns and the later forming dorsal commissure with morphogenesis of the midline glia and with the initial presence and subsequent disappearance of keratin sulfate/chondroitin sulfate glycosaminoglycans, putative boundary molecules that they have localized in this region. Enzyme digestion of the roof plate GAG's in an in vitro slice preparation will test whether dorsal column axons aberrantly cross the midline. For the studies on the DREZ, they plan first to describe the normal cellular and basal lamina elements at the CNS/PNS interface and the molecules that are expressed during the period of axonal ingrowth into the spinal cord. They will then compare these constituents with those of the DREZ in animals with crush injuries of the roots to determine if mechanical or chemical factors may contribute to regenerative failure in this region. Preliminary studies have shown that GAG's found in normal glial barriers such as the roof plate appear in reactive glia following root lesions. The putative astroglial boundary molecules of the roof plate and lesioned DREZ will be investigated in an in vitro assay system where the growing axons will be challenged with combination of putative pathway and boundary cells or molecules in various geometric patterns.

描述：（根据申请人的摘要进行了改编。） 该建议旨在比较和对比细胞和分子 星形胶质细胞可以抑制轴突生长的机制 脊髓的区域：1）屋顶板，这是瞬态 在开发过程中与背柱轴突的边界和2） 背根进入区域，该区域形成了传入的门口 开发过程中的中枢神经系统，但成为背根传感的边界 出生后再生。 申请人及其同事计划 将背侧柱的发展与后来的形成相关 与中线神经胶质形态发生的背与 角蛋白的初始存在和随后消失 硫酸盐/软骨素硫酸盐糖胺聚糖，推定的边界分子 他们已经在该地区进行了本地化。 屋顶的酶消化 体外切片制剂中的板块插科打术将测试是否背侧 圆柱轴突异常越过中线。 对于Drez的研究，他们计划首先描述正常 CNS/PNS界面的细胞和基底层元素以及 在轴突向内生长期间表达的分子 脊髓。 然后，他们将将这些成分与 DREZ在挤压根部受伤的动物中，以确定是否机械 或化学因素可能导致该地区再生失败。 初步研究表明，在正常的神经胶质屏障中发现了插科打术 例如，屋顶板出现在根部病变后反应性神经胶质中。 这 屋顶板的假定星形胶质边界分子和病变的DREZ 将在生长轴突的体外测定系统中进行研究 将通过推定途径和边界细胞的组合来挑战 或各种几何模式的分子。