Department of Cell Biology and the Centre for Neuroscience, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada.
Prog Brain Res. 2011;194:227-39. doi: 10.1016/B978-0-444-53815-4.00004-2.
Spinal cord injury is a devastating neurological trauma, often resulting in the impairment of bladder, bowel, and sexual function as well as the loss of voluntary control of muscles innervated by spinal cord segments below the lesion site. Research is ongoing into several classes of therapies to restore lost function. These include the encouragement of neural sparing and regeneration of the affected tissue, and the intervention with pharmacological and rehabilitative means to improve function. This review will focus on the application of electrical current in the spinal cord in order to reactivate extant circuitry which coordinates and controls smooth and skeletal muscle below the injury. We first present a brief historical review of intraspinal microstimulation (ISMS) focusing on its use for restoring bladder function after spinal cord injury as well as its utilization as a research tool for mapping spinal cord circuits that coordinate movements. We then present a review of our own results related to the use of ISMS for restoring standing and walking movements after spinal cord injury. We discuss the mechanisms of action of ISMS and how they relate to observed functional outcomes in animal models. These include the activation of fibers-in-passage which lead to the transsynaptic spread of activation through the spinal cord and the ability of ISMS to produce fatigue-resistant, weight-bearing movements. We present our thoughts on the clinical potential for ISMS with regard to implantation techniques, stability, and damage induced by mechanical and electrical factors. We conclude by suggesting improvements in materials and techniques that are needed in preparation for a clinical proof-of-principle and review our current attempts to achieve these.
脊髓损伤是一种严重的神经创伤,常导致损伤部位以下脊髓节段支配的膀胱、肠道和性功能障碍以及肌肉的自主控制丧失。目前正在研究几类治疗方法来恢复失去的功能。这些方法包括鼓励神经保留和受影响组织的再生,以及通过药理学和康复手段干预来改善功能。这篇综述将重点介绍电流在脊髓中的应用,以重新激活协调和控制损伤以下的平滑肌和骨骼肌的现存回路。我们首先简要回顾了脊髓内微刺激(ISMS)的应用,重点介绍了其在恢复脊髓损伤后膀胱功能方面的应用,以及作为研究工具用于映射协调运动的脊髓回路。然后,我们回顾了我们自己在使用 ISMS 恢复脊髓损伤后站立和行走运动方面的研究结果。我们讨论了 ISMS 的作用机制及其与动物模型中观察到的功能结果的关系。这些机制包括激活通路上的纤维,导致激活通过脊髓的突触传递,以及 ISMS 产生抗疲劳、承重运动的能力。我们提出了我们对 ISMS 临床潜力的看法,包括植入技术、稳定性以及机械和电因素引起的损伤。最后,我们通过建议改进材料和技术来为临床原理验证做准备,并回顾了我们目前为实现这一目标所做的努力。