FUNCTIONAL INTEGRATION OF TRANSPLANTS

这项研究的长期目标是界定 脊髓运动神经元的生理和解剖反应 (Mn)对成年大鼠脊髓损伤(SCI)的影响 确定干预行动，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 完全性横断后MNS下行输入中断 并测试胎儿脊髓(FSC) 单独移植，或与后肢锻炼相结合，将 逆转或限制脊髓损伤引起的预期反射亢进。 我们还设计了一些额外的实验来评估 脊髓功能恢复后的神经组织移植 颈部吻部或尾部的部分损伤 放大。后肢H反射的变化及诱发 刺激中脑后的后肢运动 将测试运动区(MLR)。这项建议的目标是 检查脊髓MN反射回路的时间变化和 完全性髋关节脱位术后与后肢肌肉的功能相互作用 横断性损伤为生理学检查提供了基线 对伤害的反应，所有的干预性治疗都可以 被比较。AIM II将调查短期和长期变化 尾侧至完全横断性病变的分布 传入纤维、树突形态计量学和MN大小 AIM中检测到的功能变化的解剖学相关性 I.这些措施将使用免疫细胞化学和图像 分析程序。AIM III将调查急性和 部分脊髓损伤对脑生理特性的慢性影响 H反射试验测定MNS。初始半横切 损伤(C2或T1)将为每只动物提供一侧显示 慢性影响，同时病变扩大到完全 测试前的横切面将提供单面显示 急性影响。移植所致的反射改变 干预(S)将被确定。在目标四中，有能力 神经组织移植以恢复对运动的控制 脊髓水平以下的部分颈椎SCI将被 检查过了。受伤程度的不同(C2或T1)将受到考验 对于一个完整的颈部中央图案生成器的重要性 用来诱导后肢的运动。

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.