NEUROTROPHINS AND TRANSPLANTS IN SPINAL CORD INJURY

脊髓损伤导致损伤部位神经元的丧失 以及穿过大脑的上行和下行纤维的中断， 损伤区。 我们的初步数据表明鞘内注射 胸中部挫伤后外源性BDNF的应用 刺激腰髓中脊髓回路的突触活动。 相比之下，胚胎脊髓组织和基因的移植， 工程化的成纤维细胞可用于修复解剖缺陷， 促进轴突生长。 我们建议直接 脑源性神经营养因子输注的效果是补充的热带和营养 胎儿移植物或产生神经营养素的成纤维细胞移植物的影响。 总之，输注和移植的结合将（1） 增强病变外下行纤维的伸长或发芽 或移植部位，以及（2）改善 运动功能下降控制的重要系统。 的 拟议的计划将首先最大化组织渗透和BDNF的剂量。 然后，我们将测试单个策略和组合策略的效果 应用免疫组化和束示踪法观察轴突出芽的变化。 功能恢复的生理指标将通过使用 一个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， 行为恢复的解剖和生理变化将是 使用操作定义的行为结果测量确定， 后肢运动的节段、本体脊髓和下行控制 活动 这些实验提供了一个多学科的方法， 开发脊髓损伤后功能恢复的独特策略 损伤

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.