MOTOR/SENSORY SPECIFICITY--MECHANISMS AND AUGMENTATION

运动/感觉特异性——机制和增强

• 批准号: 2038038
• 负责人: THOMAS M BRUSHART
• 金额: $ 15.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2038038
• 关键词: afferent nerve; axon; juvenile animal; laboratory rat; mature animal; motor neurons; nervous system regeneration; neurotrophic factors

Surgical repair of injured peripheral nerve often fails to restore adequate function. Misdriction of regenerating axons is a primary cause of this failure. Motor axons reaching skin provide no function and block the pathways which they occupy; cutaneous axons reaching muscle may function, but will provide incorrect information. Recent experiments suggest a possible solution to this problem. Motor axons regenerating in the rat femoral nerve produce multiple collaterals sprouts; motor/sensory specificity is improved by pruning collaterals from cutaneous nerve while keeping those in muscle nerve. Specificity may be enhanced by crushing the nerve before repair to increase collateral sprout formation and pathway sampling. If a similar effect could be produced at the time of nerve suture, the outcome of clinical nerve repair could be substantially improved. The proposed experiments are designed to further characterize the process of specificity generation through collateral pruning, and to identify techniques for its amplification which could be applied to clinical nerve repair. Aim I more clearly defines the mechanism by which nerve crush increases specificity, and seeks to correlate increased specificity with improved function. Aim II seeks to stimulate regenerative collateral sprouting of motor axons and subsequent regeneration specificityby application of trophic factors directly the repair site in a controlled manner. The function resulting from these manipulations will be correlated with regeneration specificity. These experiments open the way to direct clinical application of specificity enhancement. Aim III takes advantage of the greater specificity observed in juveniles to gain further insights into the mechanism of motor/sensory specificity, and introduces a novel nerve graft model which confornts adult pathways with juvenile axons and vice versa, to identify components which deteriorate with age. The extent of collateral sprouting in juvenile and aged rats will be correlated with final regeneration specificity. Aim IV Evidence for pruning of motor axon collaterals from cutaneous nerve has been obtained with axon tracing techniques. These experiments will seek morphologic and electrophysiologic confirmation of pruning. Aim V extends our observations of specific motor pathway characteristics to compare motor and sensory nerve as graft for regenerating motor axons. Preliminary experiments suggest that motor nerve is in fact superior, a finding which if confirmed will have immediate, direct clinical relevance.

周围神经损伤的手术修复常常失败， 恢复适当的功能。 再生轴突的误牵 这是失败的主要原因。 到达皮肤的运动轴突 不提供任何功能并阻塞它们所占据的通路; 到达肌肉的皮肤轴突可能起作用，但将提供 错误信息。 最近的实验表明， 解决方案。 大鼠运动神经轴突再生的实验研究 股神经产生多个侧枝芽;运动/感觉 通过修剪皮肤上的侧枝来提高特异性 同时保持那些在肌肉神经。 特异性可以 在修复前通过挤压神经来增强， 侧枝形成和通路取样。 如果类似的 在神经缝合时可产生效果， 可以大大提高临床神经修复的效率。 的 提出的实验旨在进一步表征 通过侧枝修剪产生特异性的过程，以及 以确定其扩增技术， 应用于临床神经修复。 目标一更明确地界定了 神经挤压增加特异性的机制，并寻求 将增加的特异性与改善的功能联系起来。 目的 II旨在刺激运动神经再生侧枝发芽 轴突和随后的再生特异性通过应用 营养因子以受控的方式直接作用于修复位点。 这些操作产生的函数将是 与再生特异性相关。 这些实验开启了 指导特异性临床应用的途径 增强 目标III利用了更大的特异性 在青少年中观察，以进一步了解 运动/感觉特异性，并介绍了一种新的神经移植物， 该模型使成年人的通路与幼年轴突相一致， 反之亦然，以识别随时间而劣化的部件。 的 幼年和老年大鼠侧支发芽的程度将 与最终再生特异性相关。 目标IV证据 用于从皮神经修剪运动轴突侧支， 用轴突追踪技术获得。 这些实验 将寻求形态学和电生理学证实， 修剪 目的V扩展了我们对特定运动的观察， 通路特征，以比较运动神经和感觉神经， 用于再生运动轴突的移植物。 初步实验 表明运动神经实际上是上级，如果 将具有即时的、直接的临床意义。