Enhancing Motor Neuron Regeneration Accuracy

提高运动神经元再生的准确性

• 批准号: 7511985
• 负责人: Roger D. Madison
• 金额: $ 8.43万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7511985
• 关键词: Adult; Animals; Axon; Axonal Transport; Back; Cholera Toxin; Colchicine; Data; Development; Distal; Dyes; Electric Stimulation; Enzyme-Linked Immunosorbent Assay; Hand; Hour; Immunohistochemistry; Injection of therapeutic agent; Injury; Intervention; Label; Laboratories; Leg; Lesion; Limb structure; Location; Mediating; Modeling; Modern Medicine; Motor; Motor Neurons; Muscle; Natural regeneration; Nerve; Nerve Crush; Nerve Regeneration; Numbers; Organ; Paralysed; Parents; Peripheral Nerves; Peripheral Nervous System; Peripheral nerve injury; Procedures; Public Health; Recovery; Recovery of Function; Risk; Rodent; Role; Sensory; Side; Signal Transduction; Site; Skin; Surgical Models; Testing; Time; United States; Wallerian Degeneration; Week; Work; axon regeneration; femoral nerve; injury and repair; preference; reinnervation; repaired; research study; retrograde transport

DESCRIPTION (provided by applicant): Preferential motor reinnervation (PMR) refers to the preference of regenerating motor neurons in a mixed peripheral nerve to reinnervate a distal terminal nerve branch to muscle rather than skin. A useful model to study PMR is the rodent femoral nerve. Proximally in the leg, motor axons are dispersed across the entire mixed nerve. Distally, the nerve divides into two approximately equal terminal branches; a motor branch to the quadriceps muscle and a purely sensory branch which continues as the saphenous nerve. Much previous work from several laboratories has shown that following a proximal lesion regenerating motor neurons preferentially, albeit incompletely, reinnervate the terminal quadriceps branch (to muscle) versus the saphenous branch (to skin). During the course of our recent studies on PMR we made a surprising observation: information from the denervated muscle is apparently rapidly conveyed to the proximal nerve lesion site and influences the subsequent accuracy of motor neuron regeneration. We have preliminary data suggesting that the delivery of this information from muscle is dependent upon active retrograde axonal transport which continues in distal denervated nerve for approximately 30 hours, or until the axon undergoes Wallerian degeneration. The experiments in this proposal build upon this unexpected observation, and will clarify the influence in denervated nerve of retrograde transport from muscle as a mechanism that influences PMR. We will use a variety of well characterized surgical models of the rodent femoral nerve to accomplish our specific aims. PUBLIC HEALTH RELEVANCE: Despite regeneration, extensive peripheral nerve injuries can result in the effective paralysis of the entire limb or distal portions of the limb such as the hands. The major key to recovery of function following nerve lesions in the peripheral nervous system is the accurate regeneration of axons to their original target end-organs. The proposed studies utilize the rodent femoral nerve and will assess the accuracy with which motor neurons project back to their original terminal nerve branch.

描述（由申请人提供）：优先运动神经再支配（PMR）是指混合周围神经中再生运动神经元优先将远端终末神经分支再支配到肌肉而不是皮肤。研究PMR的有用模型是啮齿动物股神经。在腿的近端，运动轴突分散在整个混合神经中。 在远端，神经分为两个大致相等的终末分支;一个运动分支到四头肌，一个纯粹的感觉分支作为隐神经延续。来自几个实验室的许多先前的工作已经表明，在近端损伤后，再生的运动神经元优先（尽管不完全）再神经支配终末四头肌分支（至肌肉）而不是隐肌分支（至皮肤）。在我们最近对PMR的研究过程中，我们做了一个令人惊讶的观察：来自失神经肌肉的信息显然迅速传递到近端神经损伤部位，并影响随后的运动神经元再生的准确性。我们有初步的数据表明，从肌肉传递这一信息是依赖于主动逆行轴突运输，继续在远端失神经支配的神经约30小时，或直到轴突经历沃勒变性。本实验建立在这一意外观察的基础上，将阐明逆行性神经阻滞对失神经支配神经的影响。 从肌肉转运作为一种机制，影响PMR。我们将使用各种表征良好的啮齿动物股神经手术模型来实现我们的特定目标。公共卫生相关性：尽管再生，广泛的周围神经损伤可导致整个肢体或肢体的远端部分（如手）的有效瘫痪。周围神经系统神经损伤后功能恢复的主要关键是轴突准确再生到其原始靶终末器官。拟议的研究利用啮齿动物股神经，并将评估运动神经元投射回其原始终末神经分支的准确性。