Transformation of Paraplegic Paralysis to Overground Stepping in Humans

项目摘要 越来越明显的是，瘫痪损伤下的脊髓回路具有功能潜力。 这远远超出了人们所认为的可能性。来自最近对运动完全性小鼠和大鼠的研究 瘫痪我们知道腰椎脊髓可以被神经电调制(EEMC)和 药理上(FEmc)，以实现运动控制，包括完全负重的踏步。该计划的主要目标是 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 瘫痪受试者的地面踏步。最近我们展示了四种慢性的、完全瘫痪的 个人恢复了独立站立的能力和自愿弯曲髋关节、膝盖和脚踝的能力。 当受到硬膜外刺激时。我们建议使用一种新的非侵入性方法来实现类似的结果 多点脊髓刺激策略与药物调节结合STAND和STEP 训练神经调节腰骶神经回路，使完全瘫痪的人可以恢复一些 运动功能以及随意运动。我们建议通过以下方式进一步发展这些战略 将这些干预措施与外骨骼技术相结合，使完全瘫痪的人 可以重新获得显著的社区流动性水平。我们将确定非侵入性脊柱手术的疗效 丁螺环酮(一种单胺类激动剂)的刺激和应用促进运动 在重力中性器中的活动，体重支撑在跑步机上，在Ekso上行走 机器人装置实现了瘫痪受试者在滚动式步行器中负重行走。预计 这项技术的早期开发阶段可以在临床上使用，以改善运动功能 在短短几年内。这些干预措施有可能改善健康，并可能影响 生活质量，在许多情况下，很可能导致降低医疗成本和减轻负担，不仅 对瘫痪的个人，也对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.