TRANSPLANT MEDIATED RECOVERY OF FUNCTION AFTER SPINAL CORD INJURY

脊髓损伤后移植介导的功能恢复

• 批准号: 6296931
• 负责人: Marion Murray
• 金额: $ 17.1万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-11 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296931
• 关键词: afferent nerve; age difference; axon; chordate locomotion; denervation; developmental neurobiology; disease /disorder model; electromyography; embryo /fetus cell /tissue; immunocytochemistry; in situ hybridization; innervation; laboratory rat; mature animal; nervous system regeneration; nervous system transplantation; neural plasticity; neuromuscular function; neuropharmacology; newborn animals; nonhuman therapy evaluation; serotonin; spinal cord injury; spinal cord surgery

The goal of these experiments is to analyze the behavior that develops in rats that receive fetal transplants into the site of a complete midthoracic transection at birth, to develop pharmacological approaches that may improve that behavior, and to determine the responses of cells that are axotomized by the transection. Results from our laboratory demonstrate that rats that receive these transplants develop good overground locomotion, characterized by weight support, balance, and coordination between fore and hindlimbs, which is sufficient to support locomotion even in challenging environments. Since this recovery is likely to be mediated in part by regeneration of descending systems, including the serotonergic raphe-spinal and noradrenergic coeruleo-spinal projections, we propose experiments using selected agents as a way to identify the contribution these identified systems. The effect of thee agents will be determined using motor tests that we have developed that measure contributions of weight support, balance and coordination. The morphological consequences of transections and transplants will be analyzed, using retrograde tracers and in situ hybridization with probes to regeneration associated genes, to identify which systems regenerate into or through he transplants; the cellular and molecular environment at athe transplant site will be assessed using immunocytochemical methods to identify the characteristics of environments that promote growth and integration. We will extend these studies to animals transected and given transplants at later ages, including weanling and adults, to determine the extent to which a developmental limitation may exist on the effectiveness of transplant methods. Since transplants integrate well in adults, quantitative measures should reveal recovery of some functions which may differ from those mediate by transplants into neonatal animals.

这些实验的目的是分析在这种情况下， 大鼠接受胎儿移植到一个完整的中胸的网站， 出生时横切，以开发药理学方法， 改善行为，并确定细胞反应， 被切断的轴突 我们实验室的结果表明 接受移植的老鼠在地上发育良好 以重量支撑、平衡和协调为特征的运动 在前肢和后肢之间，这足以支持运动， 在充满挑战的环境中。 由于这种复苏很可能是通过 部分是通过再生下行系统，包括肾上腺素能 中缝-脊髓和去甲肾上腺素能蓝斑-脊髓投射，我们建议， 实验使用选定的代理作为一种方式来确定的贡献 这些识别系统。 三种药剂的效果将由 使用我们开发的运动测试， 重量支撑、平衡和协调。 形态学的后果 将使用逆行示踪剂分析横断和移植 和原位杂交与探针再生相关的基因， 确定哪些系统在移植中或通过移植再生; 将评估肾移植部位的细胞和分子环境 用免疫细胞化学方法鉴定 促进增长和融合的环境。 我们将把这些研究扩展到被横切和接受移植的动物， 以后的年龄，包括断奶和成年，以确定在多大程度上， 移植的有效性可能存在发育限制， 方法. 由于移植在成人中整合良好， 应该揭示一些功能的恢复，这些功能可能与那些功能不同。 通过移植到新生动物体内来介导。