REPAIRING SENSORY PATHWAYS AFTER SPINAL CORD INJURY

脊髓损伤后修复感觉通路

• 批准号: 6540308
• 负责人: STEPHEN M ONIFER
• 金额: $ 21.6万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540308
• 关键词: afferent nerve; axon; electrophysiology; homologous transplantation; laboratory rat; nervous system regeneration; neuroanatomy; spinal cord injury; spinal ganglion; synapses

DESCRIPTION: (Adapted from the Investigator's Abstract:): This project represents a multidisciplinary approach to a long-term objective of developing a therapeutic strategy for functionally repairing the dorsal column-dorsal column nuclei sensory pathway in both acute and chronic cervical spinal cord injury (SCI). To improve upper and lower extremity function in humans with cervical SCI, it is hypothesized that injured axons need to regenerate, reinnervate their target sites, and make functional synapses with their target neurons. To test this hypothesis, we are using an adult rat model of mid-cervical SCI and are focusing on ascending primary afferent axons of forelimb dorsal root ganglia (DRG) neurons within the dorsal columns. Our preliminary anatomical and electrophysiological data suggests that some acutely injured forelimb primary afferent axons regenerate through extraspinal peripheral sciatic nerve grafts, reinnervate the brainstem, and make functional synapses with dorsal column nuclei neurons. For the Specific Aims, we will I ) use anatomical techniques to identify strategies for increasing axonal regeneration by acutely injured adult forelimb DRG neurons within sciatic nerve grafts, 2) use anatomical techniques to develop effective strategies for promoting forelimb primary afferent axonal outgrowth from sciatic nerve grafts into their target brainstem dorsal column nuclei, 3) use in vivo and in vitro electrophysiological techniques to evaluate functional synapse formation between regenerating forelimb primary afferent axons and their target dorsal column nuclei neurons as well as conditioned behavioral testing techniques to assess the effects of reconstructing the dorsal column-dorsal column nuclei sensory pathway on forelimb sensorimotor function, and 4) use the best strategies from Aims l and 2, anatomical techniques, electrophysiological techniques, and behavioral testing techniques to examine whether chronically injured forelimb primary afferent axons regenerate and form functional synapses with their target dorsal column nuclei neurons. The significance of this project is that it will delineate a novel treatment strategy for sensory dysfunction in rats with cervical SCI that, if implemented clinically, could lead to enhancement in the quality of life for persons with cervical SCI.

描述：（改编自研究者摘要：）：该项目 代表了实现发展长期目标的多学科方法 功能性修复背柱-背侧的治疗策略 急性和慢性颈脊髓的柱核感觉通路 损伤（SCI）。改善人类上肢和下肢功能 颈椎 SCI，假设受伤的轴突需要再生， 重新支配其目标位点，并与目标形成功能性突触 神经元。为了验证这一假设，我们使用成年大鼠模型 中颈 SCI 并专注于上行初级传入轴突 背柱内的前肢背根神经节（DRG）神经元。我们的 初步的解剖学和电生理学数据表明，一些急性 受伤的前肢初级传入轴突通过脊髓外再生 周围坐骨神经移植，重新支配脑干，使功能 突触与背柱核神经元。对于具体目标，我们将我） 使用解剖技术来确定增加轴突的策略 坐骨神经内急性损伤的成人前肢 DRG 神经元的再生 移植物，2) 使用解剖技术制定有效的策略 促进坐骨神经移植物的前肢初级传入轴突生长 进入其目标脑干背柱核，3）体内和体外使用 评估功能性突触形成的电生理技术 再生前肢初级传入轴突与其目标背侧之间 柱核神经元以及条件行为测试技术 评估重建背柱-背柱核的效果 感觉通路对前肢感觉运动功能的影响，4）使用最好的 目标l和2的策略、解剖技术、电生理学 技术和行为测试技术来检查是否长期 受伤的前肢初级传入轴突再生并形成功能性突触 及其目标背柱核神经元。此举的意义 该项目将描绘出一种新颖的感官治疗策略 颈椎 SCI 大鼠的功能障碍，如果临床实施，可以 从而提高颈椎 SCI 患者的生活质量。