ENHANCED PERIPHERAL NERVE REGENERATION BY DC STIMULATION

这项建议的主要目标是测试是否 体内再生轴突对微小的电场有反应， 是否在体外得到证实，以及是否有任何临床 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： 电场可以增强哺乳动物的外周神经 再生，修复过程中受到影响的步骤， 的解剖学和电生理学后果 电强化再生，参数和模式 成功的临床应用所必需的应用程序。 的 基本的方案是产生相同的双侧病变的 豚鼠腓神经并植入活性电极 一条腿是假的另一条腿是假的 手术后， 所有的数据分析都将以双盲方式进行。 通过以下方式评估每条腿的再生：功能 特殊反射的恢复，电生理记录， 推进神经前突的挤压试验， 透射电子显微镜 初步证据显示 周围神经的功能恢复速度 小电流（20微安）稳定电流可增强损伤 水流 对临床医学的影响是深远的。 任何技术能够提高率或轴突 纤维的伸长、通过瘢痕的生长或成熟将 为神经科医生提供了一个有价值的工具， 周围神经损伤 作为对哺乳动物研究的补充， 由玻璃鳍中再生的感觉纤维组成 鲶鱼 这些鱼的光学清晰度允许直接 用Nomarski光学观察再生轴突和 在体内施加电场的后果。 的大部分 关于电场对神经的影响， 从两栖动物神经突的体外研究中得知。 玻璃鲶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。 微电极将用于施加聚焦电流， 再生纤维的生长锥，以测试是否电 方向性提示可以克服自然接触引导提示 再生的纤维正常地跟随。 的精细结构 将用电子显微镜研究单个生长锥 并与其对外加电流的行为反应相关， 领域 这些研究将提供强有力的见解， 脊椎动物神经对电场的反应。

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.