PROPERTIES OF CENTRAL AXONS AT PERIPHERAL TARGETS

外周靶点中央轴突的特性

• 批准号: 3410256
• 负责人: KENNETH J. SMITH
• 金额: $ 16.63万
• 依托单位: EASTERN VIRGINIA MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3410256
• 关键词: afferent nerve; axon; denervation; dorsal root; electromyography; electron microscopy; histology; microscopy; motor neurons; myofibrils; nervous system regeneration; neurofilament; neuromuscular system; neurophysiology; peripheral nervous system; somesthesis; striated muscles; synapses; ventral roots

It is now well established that although central nerve fibers will not elongate over long distances within the adult mammalian central nervous system (CNS), they readily do so within the peripheral environment of nerves inserted into the CNS. Despite the variety of neurons with this property, there has so far been no report of whether the regenerating axons are induced by their peripheral environment and target organs to develop terminal specializations capable of sensory or motor transduction. If such receptors are formed, then peripheral nerve grafts may be of value in restoring function to limbs rendered paralysed and numb by spinal cord injury. Significantly, our preliminary experiments have established that effective synapses are formed on denervated skeletal muscle by central fibers regenerating along ventral roots replanted into the lateral column. Central nerve fibers will be led from the spinal cord via replanted ventral and dorsal roots to reinnervate either denervated skeletal muscle or denervated skin. The ventral and dorsal roots will be replanted into the ventro-lateral and dorso-lateral columns respectively, either near to their normal junction or, via a graft, to a site above the supposed location of an injury to the spinal cord. After 4-8 months the rats will be assessed physiologically and histologically to determine a) whether motor or sensory terminals have formed, b) the identities of the fibers involved, and c) whether the regenerating neurons contribute to useful motor or sensory function. Successful motor reinnervation will be assessed, in part by determining the presence of contractions of the appropriate muscles upon direct stimulation of the replanted ventral root, and upon indirect (synaptic) activation of motoneurons. The return of muscle reinnervation will also be monitored serially using EMG recordings. Successful sensory reinnervation will be determined, in part, by mapping the sensory fields of individual fibers teased from the replanted roots, and by determining the presence of central responses evoked by sensory stimulation. Another experiment will examine whether axonal damage is a prerequisite to neurite production.

现在已经很好地确定，虽然中枢神经纤维将 在成年哺乳动物体内不长距离延伸 中枢神经系统（CNS），他们很容易这样做， 插入CNS的神经的外周环境。 尽管 具有这种特性的神经元的种类，到目前为止还没有 报告再生轴突是否是由它们的 外周环境和靶器官发育终末 能够进行感觉或运动传导的专门化。 如果这样 受体形成，那么周围神经移植物可能是 对瘫痪和麻木的肢体恢复功能的价值 脊髓损伤 值得注意的是，我们的初步实验 已经确定有效的突触是在 中央纤维沿着再生的失神经骨骼肌 腹根再植到侧柱中。 中枢神经纤维将通过重新植入从脊髓引出 腹根和背根，以重新支配失神经支配的骨骼 肌肉或失神经皮肤。 腹根和背根 再植于腹外侧柱和背外侧柱 分别靠近它们的正常连接处，或者通过移植物， 脊椎受伤部位的上方 线. 4-8个月后，将对大鼠进行生理学评估 并在组织学上确定a）运动或感觉 终端已经形成，B）所涉及的纤维的身份， 以及c）再生神经元是否有助于有用的 运动或感觉功能。 成功的运动神经移植 评估，部分通过确定收缩的存在， 直接刺激移植的肌肉， 腹根，间接（突触）激活后， 运动神经元 肌肉神经再生的恢复也将是 使用EMG记录连续监测。 成功的感觉 神经的再支配将部分地通过映射感觉神经来确定。 从重新种植的根部梳理出的单个纤维的区域， 确定由感觉诱发的中枢反应的存在， 刺激. 另一项实验将研究轴突是否 损伤是神经突产生的先决条件。