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：(改编自申请人的摘要。)在中国的实验 这一建议试图比较和对比细胞和分子 星形胶质细胞抑制轴突生长的机制 脊髓区域：1)顶板，这是一个暂时性的 在发育过程中与背柱轴突的边界和2)大脑皮质的胶质穹隆 背根进入区，它形成了传入神经进入 中枢神经系统在发育过程中，但成为背根传入的边界 出生后再生。申请人和他的同事计划 背柱的发育与后期形成的关系 背侧连合与中线胶质细胞的形态发生和与 角蛋白最初的存在和随后的消失 硫酸盐/硫酸软骨素糖胺聚糖，推测的边界分子 他们已经在这个地区本地化了。屋顶的酶消化 在体外切片制备中的平板缝隙将测试背部 柱状轴突异常地穿过中线。 对于对德雷兹的研究，他们计划首先描述正常 中枢神经系统/三叉神经节界面的细胞和基板单元 在轴突向内生长期间表达的分子 脊髓。然后，他们会将这些成分与 在动物身上用挤压伤的根部来确定是否有机械性 或者，化学因素可能会导致该地区的再生能力下降。 初步研究表明，在正常的神经胶质屏障中发现了GAG 如顶板出现在根部病变后的反应性胶质细胞中。这个 顶板和受损DRIZ可能的星形胶质细胞边界分子 将在体外测试系统中进行研究，其中生长的轴突 将受到假定途径和边界细胞的组合的挑战 或各种几何图案的分子。