NEUROTROPHINS AND TRANSPLANTS IN SPINAL CORD INJURY

脊髓损伤导致损伤部位神经纤维的丢失 以及穿过上行和下行纤维的 损毁区域。我们的初步数据显示鞘内 胸中挫伤后外源性脑源性神经营养因子的应用 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上的移植 工程成纤维细胞可以用来修复解剖上的缺陷 病变空洞并促进轴突生长。我们建议直接 脑源性神经营养因子输注对营养和营养的补充作用 胎儿移植物或神经营养因子产生的成纤维细胞移植物的作用。 联合起来，输液和移植的结合将(1) 促进病变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。这个 提议的计划将首先最大限度地提高组织渗透和BDNF的剂量。 然后，我们将测试单独策略和组合策略的效果 用免疫组织化学和轨迹示踪法研究轴突萌发。 功能恢复的生理指标将通过使用 一种独特的操作条件反射范式来测试下行能力 调节后肢H反射幅度的系统。最后，这一卷 关于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度量确定 后肢运动的节段性、固有脊髓和下行控制 活动。这些实验提供了一种多学科的方法来 发展一种独特的脊髓后功能恢复策略 受伤。

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.