VESTIBULOSPINAL/SPINOCEREBELLAR PATHWAYS--TRANSPLANT MEDIATED SURVIVAL/RECOVERY

前庭脊髓/脊髓小脑通路——移植介导的生存/恢复

• 批准号: 6296932
• 负责人: ALAN R. TESSLER
• 金额: $ 17.1万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-11 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296932
• 关键词: axon; cell age; central neural pathway /tract; chordate locomotion; denervation; developmental neurobiology; disease /disorder model; embryo /fetus cell /tissue; laboratory rat; motor neurons; nervous system regeneration; nervous system transplantation; neuromuscular function; neurotrophic factors; newborn animals; spinal cord injury; spinal cord surgery; spinal reflex; vestibular pathway

Transplants of embryonic spinal cord can improve locomotor function after experimental spinal cord injuries. To study the responsible mechanisms we propose experiments that will investigate Clarke's nucleus (CN) and vestibulospinal neurons. These neurons form the afferent and efferent limbs of circuits that are crucial for posture and gait stability and important for coordination between forelimbs and hindlimbs during locomotion. Our previous studies with embryonic CNS tissues suggest that the neurotrophic factor Neurotrophin-3 (NT-3) can rescue axotomized CN neurons from retrograde cell death. One series of studies will determine whether the exogenous administration of NT-3 by genetically modified cells rescues axotomized CN neurons. Cell lines have the additional potential to promote axon regeneration in the adult CNS (Specific Aim 1). Axotomized neurons may contribute to recovery through collateral axons. This capacity would be enhanced if stripping of preterminal synapses (desynapsis) which ordinarily accompanies axotomy were prevented or reversed. A second series of experiments will examine whether transplants of embryonic spinal cord can prevent or reverse desynapsis in axotomized CN neurons (Specific Aim 2). Transplant-mediated improvement in locomotor function has not been related to specific axon pathways. A third series of studies will determine whether transplants can mediate recovery of VST function after spinal cord injury. interruption of the vestibulospinal tract (VST) produces obvious and quantifiable behavioral deficits (Specific Aim 3). Relating recover to tahe actions of this pathway will be an important step in understanding recovery and for devising strategies to enhance recovery.

胚胎脊髓移植可改善术后运动功能 实验性脊髓损伤。 为了研究责任机制，我们 提出研究克拉克核（CN）的实验和 前庭脊髓神经元。 这些神经元形成传入神经元和传出神经元 对于姿势和步态稳定性至关重要的电路肢体 对于前肢和后肢之间的协调非常重要 运动。 我们之前对胚胎中枢神经系统组织的研究表明 神经营养因子 Neurotropin-3 (NT-3) 可以挽救轴突断裂的 CN 逆行细胞死亡的神经元。 一系列研究将确定 是否通过转基因细胞外源施用NT-3 拯救轴突切断的 CN 神经元。 细胞系具有额外的潜力 促进成人中枢神经系统的轴突再生（具体目标 1）。 轴切 神经元可能通过侧支轴突促进恢复。 这个容量 如果剥离前末端突触（去突触），则会得到增强 通常伴随轴切术的发生可以被预防或逆转。 第二个系列 实验将检查胚胎脊髓移植是否 可以预防或逆转轴突 CN 神经元的去突触（具体目标 2）。 移植介导的运动功能改善尚未被证实 与特定的轴突通路有关。 第三系列研究将 确定移植后是否可以介导 VST 功能的恢复 脊髓损伤。前庭脊髓束中断 (VST) 产生明显且可量化的行为缺陷（具体目标 3）。 将恢复与该途径的作用联系起来将是重要的一步 了解恢复并制定促进恢复的策略。