RECOVERY OF FUNCTION AFTER SPINAL CORD DAMAGE

本方案项目的重点是负责恢复的机制， 脊髓损伤后的运动功能和操作， 提高回收率我们在上一次授予期间进行的研究 这些时期表明，恢复功能可能不需要 重建原有的脊髓回路有限再生 与其他补偿性反应一起可能就足够了。 个人 本计划项目中的项目将检查以下相关因素： 在特定分子、突触、电路和神经元水平上的运动恢复 生物力学系统 在一个项目中，我们将检查的机制， 胚胎脊髓移植能改善大鼠的运动功能 脊髓完全横断 这种现象的生理基础 回收率将被定量分析和操纵。 这些研究将使我们能够区分对复苏的贡献 由脊髓上和脊髓本体系统和那些由 在横断和移植的尾部重组脊髓。 在 Tessler的项目，我们将确定是否确定神经营养因子 通过转基因细胞传递到受损的大鼠脊髓， 增强轴突切断的Clarke核的存活和再生， 神经元，以及移植是否可以让这些细胞保持其 正常电路。 在大鼠前庭脊髓神经元中， Tessler的项目和金鱼Mauthner细胞将在Faber的研究 我们将研究自发再生与 或通过移植和运动行为介导的再生 识别出脑干神经元的集合。 在Fischer的项目中， 体内和体外实验将通过以下方法研究分子机制： 切断轴突的成年大鼠背根神经节神经元改变了 轴突变化时细胞骨架蛋白的表达和转运 从稳定的结构到活跃的生长过程。 了解这些 机制将有助于制定干预措施， CNS轴突的再生。 这些项目将提供 关于功能恢复的性质和程度的定量信息 在几种不同的模型中。 审查的程度和限制 再生到中枢神经系统，并建议治疗干预， 加强恢复。

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.