RECOVERY OF FUNCTION AFTER SPINAL CORD DAMAGE

本计划项目侧重于解决以下问题的机制 脊柱损伤后的运动功能和可以 加强回收我们在上一次批出款项时进行的研究 一些时期表明，恢复功能可能不需要 有限再生原脊髓环路的重建 与其他补偿性反应一起可能就足够了。个体 本计划项目中的项目将检查以下各项的相关性 在特定分子、突触、回路和 生物力学系统。在一个项目中，我们将通过以下方式检查这些机制 胚胎脊髓移植对大鼠运动功能的改善作用 有完整的脊髓横断。这一现象的生理基础 恢复率将进行定量分析和药理学操作。 这些研究将使我们能够区分对恢复的贡献 由脊柱上和固有脊髓系统制作的，以及由 将脊髓尾端重组为横断和移植。在……里面 泰斯勒的项目我们将确定已识别的神经营养因子 通过转基因细胞传递到损伤的大鼠脊髓可以 增强轴突切断后克拉克核的存活和再生， 神经元，以及移植能否使这些细胞保持其 正常电路。在大鼠前庭脊髓神经元中的研究 泰斯勒计划和将在费伯氏实验室研究的金鱼毛特纳细胞 我们将研究自发再生之间的关系 或通过移植促进再生，并通过 确定了几组脑干神经元。在费舍尔的并行项目中 体内和体外实验将通过以下方式研究分子机制 切断成年大鼠背根神经节神经元后， 细胞骨架蛋白在轴突改变时的表达和转运 从稳定的结构到积极增长的过程。了解这些 机制将有助于制定干预措施，以加强 中枢神经系统轴突的再生。这些项目加在一起将提供 关于功能恢复的性质和程度的定量信息 有几种不同的型号。检查的范围和限制 再生到中枢神经系统，并提出治疗干预措施 加大回收力度。

This Program Project focuses on mechanisms which account for recovery of locomotor function following spinal injury and on manipulations which can enhance the recovery Our studies carried out during previous granting periods have indicated that restoration of function may not require reestablishment of the original spinal circuitry limited regeneration together with other compensatory responses may suffice. Individual projects in the present Program Project will examine the correlates of motor recovery at the levels of specific molecules, synapses, circuits, and biomechanical systems. In a Project we will examine the mechanisms by which transplants of embryonic spinal cord improve motor function in rats with complete spinal cord transections. The physiologic basis of this recovery will be analyzed quantitatively and manipulated pharmacologically. These studies will allow us to distinguish the contributions to recovery made by supraspinal and propriospinal systems and those made by the reorganizing spinal cord caudal to the transection and transplant. In Tessler's Project we will determine whether identified neurotrophic factors delivered to the injured rat spinal cord by genetically modified cells can enhance the survival and regeneration of axotomized Clarke's nucleus, neurons, and whether transplants can allow these cells to maintain their normal circuitry. In rat vestibulospinal neurons to be studied in Tessler's Project and in goldfish Mauthner cells to be studied in Faber's Project we will examine the relationship between spontaneous regeneration or regeneration assisted by transplants and motor behaviors mediated by identified sets of brainstem neurons. In Fischer's Project parallel in vivo and in vitro experiments will examine the molecular mechanisms by which axotomized adult rat dorsal root ganglion neurons modify the expression and transport of cytoskeletal proteins as their axons change from stable structures to actively growing processes. Understanding these mechanisms will contribute to developing interventions that can enhance the regeneration of CNS axons. These projects together will provide quantitative information on the nature and extent of recovery of function in several different models. examine the extent and constraints on regeneration into the CNS and suggest therapeutic interventions that will enhance recovery.