Transformation of Paraplegic Paralysis to Overground Stepping in Humans

人类截瘫向地上行走的转变

• 批准号: 10241521
• 负责人: REGGIE EDGERTON
• 金额: $ 54.87万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241521
• 关键词: Agonist; Ankle; Awareness; Body Weight; Buspirone; Chronic; Clinic; Communities; Cutaneous; Development; Devices; Diagnosis; Electrodes; Family Caregiver; Force of Gravity; Generations; Goals; Health; Health Care Costs; Hip region structure; Human; Individual; Injury; Intervention; Knee; Lead; Lesion; Locomotion; Lower Extremity; Mediating; Motion; Motor; Motor Activity; Movement; Mus; Musculoskeletal Equilibrium; Neurostimulation procedures of spinal cord tissue; Outcome; Painless; Paralysed; Paraplegia; Performance; Pharmacology; Probability; Property; Quality of life; Rattus; Recovery; Recovery of Function; Sensory; Series; Site; Speed; Spinal; Spinal Cord; Spinal Injuries; Spinal cord injury; Spinal cord injury patients; Step training; Technology; Training; Volition; Walkers; Weight-Bearing state; connectome; cost; effectiveness evaluation; exoskeleton; exoskeleton device; experience; experimental study; improved; insight; limb movement; motor control; motor function improvement; motor function recovery; neuroregulation; novel; relative effectiveness; robot assistance; robotic device; technology development; tool; treadmill

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.

项目概要 越来越明显的是，瘫痪损伤下方的脊髓回路具有功能潜力 这远远超出了人们的想象。根据最近对具有运动功能的小鼠和大鼠的研究 我们知道腰骶脊髓可以进行电神经调节（eEmc）并且 药理学（fEmc）以实现运动控制，包括完全负重步进。该组织的主要目标是 该项目是开发非侵入性多重神经调节策略，以促进完全负重 瘫痪受试者的地面行走。最近我们证明了四种慢性、完全瘫痪的患者 个体重新获得独立站立的能力以及自愿弯曲臀部、膝盖和脚踝的能力 当受到硬膜外刺激时。我们建议使用新型非侵入性方法来实现类似的结果 多部位脊髓刺激策略与站立和步骤的药理调节相结合 进行神经调节腰骶回路的训练，以便完全瘫痪的人可以恢复一些能力 运动功能以及随意运动。我们建议通过以下方式进一步制定这些战略： 将这些干预措施与外骨骼技术相结合，使完全瘫痪的人 可以重新获得显着水平的社区流动性。我们将确定无创脊柱治疗的有效性 刺激和给予丁螺环酮（一种单胺能激动剂）治疗以促进运动 在重力中性装置中的活动、在跑步机上支撑体重的踩踏以及在 EKSO 中的踩踏 机器人装置可让瘫痪受试者在滚动助行器中实现完全承重行走。预计 该技术开发的早期阶段可在诊所内使用，以改善运动功能 几年之内。这些干预措施有可能改善健康，并可能影响 生活质量，并且在许多情况下，可能不仅会降低人们的健康成本和负担 瘫痪者，也包括他们的家人和护理人员。