Transformation of Paraplegic Paralysis to Overground Stepping in Humans

项目摘要 越来越明显的是，瘫痪性损伤下方的脊髓回路具有功能潜力 这远远超过了人们所认为的可能性。从最近的研究小鼠和大鼠的运动完全 我们知道腰骶脊髓可以被电神经调节（eEmc）， 控制器（fEmc），以实现电机控制，包括全承重步进。的主要目标 该项目是开发非侵入性的多种神经调节策略，以促进完全负重 在地上踩瘫痪的人最近我们证明了四个慢性的，完全瘫痪的 患者恢复了独立站立的能力和主动弯曲髋关节、膝关节和踝关节的能力 当受到精神刺激时。我们建议使用一种新的非侵入性的方法来实现类似的结果。 多部位脊髓刺激策略与站立和步进的药理学调节一致 训练神经调节腰骶回路，使完全瘫痪的人可以恢复一些 运动功能以及自主运动。我们建议进一步发展这些策略， 将这些干预措施与外骨骼技术相结合， 可以重新获得显著的社区流动性。我们将确定非侵入性脊柱 促进运动丁螺环酮（单胺能激动剂）治疗的刺激和给药 在重力中性装置中的活动，在跑步机上行走的体重支撑，以及在EKSO中行走 机器人设备，以实现在滚动步行者中瘫痪受试者的完全负重行走。预计各国 该技术的早期发展阶段可以在临床上用于改善运动功能 在几年之内。这些干预措施有可能改善健康状况，并可能影响 生活质量，在许多情况下，可能导致降低卫生费用和减轻负担，不仅是对 瘫痪的人，也是他们的家人和照顾者。

Project Summary It is becoming increasingly evident that the spinal circuitries below a paralyzing injury have a functional potential that far exceeds what has been thought to be possible. From recent studies in mice and rats with motor complete paralysis we know that the lumbosacral spinal cord can be neuromodulated electrically (eEmc) and pharmacologically (fEmc) to enable motor control, including full weight-bearing stepping. The main goal of the project is the development of noninvasive multiple neuromodulatory strategies to facilitate full weight bearing overground stepping in paralyzed subjects. Recently we demonstrated that four chronic, completely paralyzed individuals regained the ability to stand independently and the ability to voluntarily flex the hip, knee, and ankle when being stimulated epidurally. We propose to accomplish similar outcomes using a novel noninvasive multi-site spinal cord stimulation strategy in concert with pharmacological modulation with stand and step training to neuromodulate the lumbosacral circuitry so that completely paralyzed individuals can regain some locomotor function as well as voluntary movements. We propose to develop these strategies further by combining these interventions with an exoskeleton technology so that individuals with complete paralysis can regain significant levels of community mobility. We will determine the effectiveness of noninvasive spinal stimulation and administration of buspirone (a monoaminergic agonist) treatment for facilitating of locomotor activity in the gravity-neutral apparatus, body weight supported stepping on a treadmill, and stepping in the EKSO robotic device to achieve full weight bearing stepping in paralyzed subjects in rolling walker. It is anticipated that the early stages of development of this technology could be available within the clinic to improve motor function within a matter of a few years. These interventions have the potential to improve health, and can impact the quality of life and, in many cases, can likely to lead to reduced health costs and a lower burden not only to the paralyzed individuals, but also to their families and caregivers.