FUNCTIONAL INTEGRATION OF TRANSPLANTS

本研究的长期目标是确定 脊髓运动神经元的生理解剖反应 (MN)脊髓损伤（SCI）在成年大鼠，和 确定干预措施，如神经移植， 手术，可以导致脊髓功能的恢复。 实验的目的是评估的后果， 完全横断后MN下行输入中断 并测试胎儿脊髓（FSC） 单独移植或结合后肢锻炼， 逆转或限制SCI引起的预期反射亢进。 设计了额外的实验来评估以下因素的影响： 神经组织移植对脊髓功能恢复的影响 颈部头部或尾部的部分损伤 放大后肢H反射的变化和诱导 刺激中脑后的后肢运动 将测试运动区（MLR）。本提案的目标一将 检查脊髓MN反射回路的时间变化， 功能相互作用后，后肢肌肉完全 横断病变，为生理学检查提供基线 对损伤的反应，所有干预性治疗都可以 被比较。Aim II将调查短期和长期变化 分布在完全横断病变的尾部， 传入纤维，树突形态和MN大小，以提供一个 Aim中检测到的功能变化的解剖学相关性 I.这些措施将利用免疫细胞化学和图像 分析程序。目的III将研究急性和 部分SCI对生理特性的慢性影响 MN，通过H反射测试确定。初始半切 病变（C2或T1）将为每只动物提供一侧， 慢性影响，而扩大病变到一个完整的 测试前的横切将提供一侧显示 急性效应。移植引起的反射改变 将确定干预措施。在目标四中， 神经组织移植，以恢复运动控制， 部分颈脊髓损伤水平以下的脊髓将被 考察损伤水平（C2或T1）的差异将测试 一个完整的宫颈中央模式发生器的重要性 用于诱导后肢的运动。

The long-term objectives of this study are to define the physiological and anatomical responses of spinal cord motoneurons (MN) to spinal cord-injury (SCI) in the adult rat, and to determine if interventive actions, such as neurotransplantation procedures, can lead to restoration of spinal cord function. Experiments are designed to evaluate the consequences of interruption of descending input to MNs after complete transection of the spinal cord and to test whether a fetal spinal cord (FSC) transplant alone, or in combination with hindlimb exercise, will reverse or limit the expected hyperreflexia resulting from SCI. Additional experiments are designed to evaluate the influence of neural tissue transplants on return of spinal cord function after a partial injury either rostral or caudal to the cervical enlargement. Changes in the H-reflex in hindlimbs and induction of hindlimb locomotion following stimulation of the mesencephalic locomotor region (MLR) will be tested. Aim I of this proposal will examine temporal changes in spinal cord MN reflex circuitry and functional interaction with hindlimb muscles after a complete transection lesion to provide a baseline for the physiological responses to injury, against which all interventive treatments can be compared. Aim II will investigate short- and long-term changes caudal to a complete transection lesion in the distribution of afferent fibers, dendritic morphometry and MN size to provide an anatomical correlation to the functional changes detected-in Aim I. These measures will be made using immunocytochemical and image analysis procedures. Aim III will investigate the acute and chronic effects of a partial SCI on physiological properties of MNs, as determined by H-reflex testing. Initial hemisection lesions (at C2 or T1) will provide one side per animal displaying chronic effects, while enlargement of the lesion to a complete transection just prior to testing will provide one side displaying acute effects. Reflex modifications resulting from transplantation intervention(s) will be determined. In Aim IV, the capacity for neural tissue transplants to restore locomotor control to the spinal cord below the level of a partial cervical SCI will be examined. Differences in the level of injury (C2 or T1) will test for the importance of an intact cervical central pattern generator for inducing locomotion of the hindlimbs.