ENHANCED PERIPHERAL NERVE REGENERATION BY DC STIMULATION

通过直流刺激增强周围神经再生

• 批准号: 3477442
• 负责人: MICHAEL E MCGINNIS
• 金额: $ 8.05万
• 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/3477442
• 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.

这项提议的广泛目标是测试 体内再生的轴突对微小电场的反应 已经在体外得到证实，以及是否有临床上 外加电流作为治疗工具的相关性 周围神经损伤。这个项目将建立：学位 电场可以增强哺乳动物的周围神经 再生，修复过程中受影响的步骤， 颈椎病的解剖和电生理后果 电强化再生，以及参数和模式 成功的临床应用所必需的应用。这个 基本方案是产生完全相同的双侧病变 豚鼠腓神经及植入活性电极的实验研究 一条腿是假的，另一条是假的。手术，随后的 评估，所有数据分析都将双盲进行。 每条腿的再生评估将由：功能性 恢复特定反射、电生理记录、 前移神经前额的挤压试验，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 小电流(20微安)稳定的电击可以加强伤害 洋流。这对临床医学的影响是深远的。 任何能够提高轴突比率的技术 纤维的伸长、通过疤痕生长或成熟将 为神经科医生提供了一种有价值的工具 周围神经损伤。 作为哺乳动物研究的补充，观察结果将是 由玻璃鳍片中再生的感觉纤维制成 鲶鱼。这些鱼的光学清晰度允许直接 再生轴突的Nomarski光学观察 活体内外加电场的后果。很大一部分是 已知的电场对神经的影响 从两栖类神经突起发育的体外研究中学到的。 玻璃鱼提供了一个独特的机会来测试一些 这些关于成体体内再生纤维的概念。 微电极将被用于将聚焦电流施加到 测试再生纤维的生长锥体是否带电 定向线索可以克服自然接触引导线索 再生纤维通常会随之而来。An的精细结构 单个生长锥将用电子显微镜进行研究。 并与其对外加电子的行为反应相关联 菲尔德。这些研究将为我们提供对 脊椎动物神经对电场的反应。