ENHANCED PERIPHERAL NERVE REGENERATION BY DC STIMULATION

通过直流刺激增强周围神经再生

基本信息

批准号：
3477445
负责人：
MICHAEL E MCGINNIS
金额：
$ 9.28万
依托单位：
SPELMAN COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-08-01 至 1994-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3477445
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 transmission electron microscopy

项目摘要

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.

该提议的广泛目的是测试是否体内再生轴突对微小电场的反应在体外证明，是否有临床应用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外周神经再生，受影响的维修过程的步骤，解剖学和电生理后果电气增强的再生以及参数和模式成功的临床应用所必需的申请。这基本方案是产生相同的双侧病变豚鼠中的孔神经并植入活性电极一条腿，另一只腿。手术，随后评估和所有数据分析将进行双盲。每条腿的再生评估将是：功能恢复特定反射，电生理记录，捏钉测试，用于前进神经方面，以及光线和光线透射电子显微镜。初步证据表明从外周神经恢复的功能恢复速率可以通过小（20微型）稳定的电气来增强伤害电流。对临床医学的影响是深远的。任何能够增强轴突速率的技术延伸，通过疤痕或纤维成熟的增长将提供有价值的神经科医生的工具周围神经损伤。作为哺乳动物研究的辅助，观察将是由玻璃鳍中的感官纤维制成鲶鱼。这些鱼的光学清晰度允许直接用Nomarski的观察轴突和体内应用电场的后果。什么是已经知道电场对神经的影响从开发两栖神经突的体外研究中学到的东西。玻璃cat鱼提供了一个独特的机会来测试一些这些关于体内成人再生纤维的概念。微电极将用于将聚焦电流应用于再生纤维的生长锥以测试是否电气方向提示可以克服自然接触指导提示通常随之而来的再生纤维。一个精美的结构将使用电子显微镜研究个体生长锥并与其对应用电气的行为反应相关场地。这些研究将为您提供有力的见解脊椎动物对电场的反应。