NEUROTROPHINS AND TRANSPLANTS IN SPINAL CORD INJURY

脊髓损伤中的神经营养因子和移植物

• 批准号: 6187127
• 负责人: BRADFORD T STOKES
• 金额: $ 24.6万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6187127
• 关键词: embryo /fetus tissue transplantation; fibroblasts; gene therapy; immunocytochemistry; laboratory rat; nervous system regeneration; nervous system transplantation; neuronal guidance; neurotrophic factors; operant conditionings; psychomotor function; spinal cord injury

Spinal cord injury results in the loss of neuropil at the injury site and disruption of ascending and descending fibers that pass through the lesioned area. Our preliminary data suggests that intrathecal administration of exogenous BDNF after a mid-thoracic contusion injury stimulates the synaptic activity of spinal circuits in the lumbar cord. In contrast, transplants of fetal spinal cord tissue and genetically engineered fibroblasts can be used to repair the anatomical deficit at the lesion cavity and promote axonal growth. We propose that the direct effects of BDNF infusion are complementary to the tropic and trophic effects of fetal grafts or neurotrophin producing fibroblast grafts. Together, the combination of infusion and transplantation will (1) enhance elongation or sprouting of descending fibers beyond the lesion or transplantation site and (2) improve the functional activity of systems important for descending control of motor function. The proposed plan will first maximize tissue penetration and dosage of BDNF. We will then test the effects of the individual and combined strategies on axonal sprouting using immunohistochemical and tract tracing methods. Physiological indices of functional recovery will be assessed by using a unique operant conditioning paradigm to test the ability of descending systems to modulate hindlimb H-reflex amplitude. Finally, the roll of anatomical and physiological changes on behavioral recovery will be determined using operationally defined behavioral outcome measures of segmental, propriospinal, and descending control of hindlimb motor activity. These experiments provide a multidisciplinary approach to developing a unique strategy for functional recovery after spinal cord injury.

脊髓损伤导致损伤部位的神经肽丧失 并破坏通过 病变区域。 我们的初步数据表明鞘内 胸骨挫伤后施用外源性BDNF 刺激腰部脊柱中脊柱的突触活动。 相反，胎儿脊髓组织的移植和遗传学 工程化的成纤维细胞可用于修复解剖缺陷 病变腔并促进轴突生长。 我们建议直接 BDNF输注的影响与热带和营养互补 胎儿移植物或神经营养蛋白产生成纤维细胞移植物的作用。 一起，输注和移植的组合将（1） 增强病变以外的降纤维的伸长或发芽 或移植位点，（2）改善 系统对于降低电机功能的控制很重要。 这 拟议的计划将首先最大化组织渗透和BDNF的剂量。 然后，我们将测试个人和组合策略的影响 使用免疫组织化学和道追踪方法进行轴突发芽。 功能恢复的生理指标将通过使用 独特的操作调节范式测试下降的能力 调节后肢H反射振幅的系统。 最后，卷 行为恢复的解剖学和生理变化将是 使用操作定义的行为结果测量 后肢电机的节段，天前和下降的控制 活动。 这些实验提供了一种多学科的方法 制定脊髓后功能恢复的独特策略 受伤。