ENHANCED PERIPHERAL NERVE REGENERATION BY DC STIMULATION

通过直流刺激增强周围神经再生

• 批准号: 3477440
• 负责人: MICHAEL E MCGINNIS
• 金额: $ 10.42万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 1993-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477440
• 关键词: afferent nerve; axon; catfish; electron microscopy; electrophysiology; electrostimulus; guinea pigs; microelectrodes; microscopy; nervous system regeneration; neuroanatomy; neurosurgery; peripheral nervous system; reflex; scanning electron microscopy

The broad objective of this proposal is to test whether regenerating axons in vivo respond to minute electric fields as has been demonstrated in vitro and whether there is any clinical relevance of applied electric currents as a therapeutic tool for peripheral nerve injuries. This project will establish: the degree to which electric fields can enhance mammalian peripheral nerve regeneration, the steps of the repair process that are affected, the anatomical and electrophysiological consequences of electrically enhanced regeneration, and the parameters and modes of application necessary for successful clinical applications. The basic protocol is to produce identical bilateral lesions of the peroneal nerves in guinea pigs and to implant an active electrode in one leg and a sham in the other. The surgery, subsequent evaluations, and all data analysis will be done double-blind. Assessment of regeneration in each leg will be by: functional recovery of specific reflexes, electrophysiological recordings, the pinch test for advancing nerve fronts, and both light and transmission electron microscopy. Preliminary evidence indicates that the rate of functional recovery from a peripheral nerve injury can be enhanced by small (20 microamp) steady electric currents. The implications for clinical medicine are profound. Any technique capable of enhancing the rate of either axonal elongation, growth through the scar, or maturation of fibers will provide a valuable tool of neurologists faced with proximal peripheral nerve injuries. As an adjunct to the mammalian studies, observations will be made of regenerating sensory fibers in the fins of the glass catfish. The optical clarity of these fish allows for direct observation with Nomarski optics of regenerating axons and the consequences of applied electric fields in vivo. Much of what is known about the effects of electric fields on nerves has been learned from in vitro studies of developing amphibian neurites. The glass catfish provides the unique opportunity to test some of these notions on adult regenerating fibers in vivo. Microelectrodes will be used to apply focused electric currents to the growth cone of regenerating fibers to test whether electrical directional cues can overcome the natural contact guidance cues the regenerating fibers normally follow. The fine structure of an individual growth cone will be studied with electron microscopy and correlated with its behavioral response to an applied electric field. These studies will provide powerful insights into the response of vertebrate nerves to electric fields.

该提案的主要目标是测试是否 体内再生轴突对微小电场的反应与以前一样 已在体外得到证实，是否有临床效果 施加电流作为治疗工具的相关性 周围神经损伤。 该项目将建立： 学位 电场可以增强哺乳动物的周围神经 再生，受影响的修复过程的步骤， 的解剖学和电生理学后果 电强化再生及其参数和模式 成功的临床应用所必需的应用。 这 基本方案是产生相同的双侧病变 豚鼠的腓神经并植入有源电极 一条腿上有假肢，另一条腿上有假肢。 手术后， 评估和所有数据分析都将进行双盲。 每条腿的再生评估将通过以下方式进行： 功能性 恢复特定反射、电生理记录、 推进神经前部的捏测试，以及光和 透射电子显微镜。 初步证据表明 周围神经的功能恢复率 小型（20微安）稳定电流可以增强伤害 电流。 对临床医学的影响是深远的。 任何能够提高任一轴突速率的技术 伸长、通过疤痕生长或纤维成熟将 为面临近端疾病的神经科医生提供了一个有价值的工具 周围神经损伤。 作为哺乳动物研究的辅助手段，观察将 由玻璃翅片中的再生感觉纤维制成 鲶鱼。 这些鱼的光学清晰度允许直接 用Nomarski光学器件观察再生轴突和 体内施加电场的后果。 很多是什么 人们已经知道电场对神经的影响 从发育两栖动物神经突的体外研究中获悉。 玻璃鲶鱼提供了独特的机会来测试一些 这些关于成人体内再生纤维的概念。 微电极将用于施加聚焦电流 再生纤维的生长锥，测试是否带电 方向提示可以克服自然接触引导提示 再生纤维通常随之而来。 的精细结构 将用电子显微镜研究单个生长锥 并与其对所施加的电的行为反应相关 场地。 这些研究将为我们提供强有力的见解 脊椎动物神经对电场的反应。