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: 6393905
• 负责人: BRADFORD T STOKES
• 金额: $ 25.34万
• 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/6393905
• 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神经纤维丢失 以及穿过的上升和下降纤维的破坏 病变区域。 我们的初步数据表明鞘内注射 胸椎中部挫伤后给予外源性 BDNF 刺激腰脊髓脊髓回路的突触活动。 相比之下，胎儿脊髓组织和基因移植 工程化成纤维细胞可用于修复解剖缺陷 损伤空腔并促进轴突生长。 我们建议直接 BDNF 输注的效果与热带和营养性效果互补 胎儿移植物或产生神经营养蛋白的成纤维细胞移植物的影响。 输注和移植相结合将 (1) 增强病灶外下行纤维的伸长或发芽 或移植部位（2）提高功能活性 对于运动功能的下降控制很重要的系统。 这 拟议的计划首先将最大限度地提高 BDNF 的组织渗透性和剂量。 然后我们将测试单独策略和组合策略的效果 使用免疫组织化学和纤维束追踪方法观察轴突出芽。 功能恢复的生理指标将通过使用进行评估 独特的操作性条件反射范式来测试下降的能力 调节后肢 H 反射幅度的系统。 最后，一卷 行为恢复的解剖学和生理学变化将 使用可操作定义的行为结果测量来确定 后肢运动的节段、本体脊髓和下降控制 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。