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: 6273764
• 负责人: Marion Murray
• 金额: $ 17.1万
• 依托单位: ALLEGHENY UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 1998-11-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273764
• 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.

这些实验的目标是分析在 接受胚胎移植到完整的中胸部位的大鼠 出生时横切，以开发药理学方法，可能 改善这种行为，并确定细胞对 被横切术切断的轴突。我们实验室的结果表明 接受这些移植的大鼠在地上发育良好 以负重、平衡和协调为特征的运动 前肢和后肢之间，这足以支持甚至运动 在充满挑战的环境中。由于这一复苏很可能是通过 部分是通过下行系统的再生，包括5-羟色胺能 中缝-脊髓和去甲肾上腺素能蓝斑-脊髓投射 使用选定的代理作为确定贡献的一种方式的实验 这些已识别的系统。这三个特工的作用将会被确定 使用我们开发的马达测试来测量 负重支撑、平衡和协调。形态上的后果 将使用逆行示踪剂对横切和移植进行分析 与再生相关基因的探针进行原位杂交，以 确定哪些系统通过移植或通过移植再生； 将评估移植部位的细胞和分子环境 用免疫细胞化学方法鉴定细胞的特征 促进增长和融合的环境。 我们将把这些研究扩展到动物的横切和移植。 后期，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：研究方法。由于移植在成人中很好地融合，量化措施 应该显示出某些功能的恢复，这些功能可能与 通过移植到新生动物体内进行调解。