FUNCTIONAL INTEGRATION OF TRANSPLANTS

移植物的功能整合

• 批准号: 6241371
• 负责人: ROBERT D SKINNER
• 金额: $ 19.12万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241371
• 关键词: acute disease /disorder; afferent nerve; chordate locomotion; chronic disease /disorder; electromyography; electronic stimulator; exercise; immunocytochemistry; laboratory rat; motor neurons; nervous system regeneration; nervous system transplantation; neuroanatomy; serotonin; spinal cord injury; spinal reflex

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.

本研究的长期目标是确定 脊髓运动神经元的生理和解剖反应 （MN）对成年大鼠的脊髓损伤（SCI），以及 确定是否采取干预措施，例如神经移植 手术，可以导致脊髓功能的恢复。 实验旨在评估以下后果 完全横断后 MN 的下行输入中断 脊髓并测试是否有胎儿脊髓（FSC） 单独移植或与后肢锻炼相结合，将 逆转或限制 SCI 引起的预期反射亢进。 额外的实验旨在评估 神经组织移植后脊髓功能恢复 颈椎头侧或尾侧的部分损伤 放大。后肢 H 反射的变化和诱导 中脑刺激后后肢运动 将测试运动区域（MLR）。该提案的目标一是 检查脊髓 MN 反射回路的时间变化 完成后与后肢肌肉的功能相互作用 横断损伤为生理学提供基线 对伤害的反应，所有干预治疗都可以针对这种反应 进行比较。目标 II 将调查短期和长期变化 尾部至完全横断病变的分布 传入纤维、树突形态测量和 MN 大小以提供 与 Aim 中检测到的功能变化的解剖相关性 I. 这些措施将使用免疫细胞化学和图像来进行 分析程序。目标 III 将调查急性和 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（在 C2 或 T1）将提供每只动物展示的一侧 慢性影响，同时病变扩大至完全 测试前的横断面将提供一侧显示 急性影响。移植引起的反射改变 将确定干预措施。在目标 IV 中，能力 神经组织移植以恢复运动控制 部分颈椎 SCI 水平以下的脊髓将 检查了。将测试伤害级别（C2 或 T1）的差异 完整的颈部中央模式发生器的重要性 用于诱导后肢运动。