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: 5215248
• 负责人: ALAN R. TESSLER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5215248
• 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脊髓损伤后的运动功能 实验性脊髓损伤 为了研究我们所研究的 提出研究克拉克核（CN）的实验， 前庭脊髓神经元 这些神经元形成传入和传出 对姿势和步态稳定性至关重要的电路分支， 在运动过程中，前肢和后肢之间的协调非常重要 运动 我们以前对胚胎中枢神经系统组织的研究表明， 神经营养因子神经营养素-3（NT-3）可以挽救切断轴突的CN 神经元逆行性细胞死亡 一系列的研究将决定 通过遗传修饰的细胞外源性施用NT-3是否 拯救轴突切断的CN神经元。 细胞系具有额外的潜力， 促进成年CNS中的轴突再生（具体目标1）。 轴突切开 神经元可能有助于通过侧支轴突恢复。 这种能力 将增强，如果剥离的前终末突触（突触消失）， 通常伴随轴突切断术被阻止或逆转。 第二系列 实验将检验胚胎脊髓的移植 可以防止或逆转轴突切断的CN神经元中的突触不连（Specific Aim 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 确定移植是否可以介导VST功能的恢复， 脊髓损伤前庭脊髓束阻断术 产生明显和可量化的行为缺陷（具体目标3）。 将恢复与这条途径的行动联系起来将是重要的一步 在理解复苏和制定战略，以加强复苏。