Rehabilitation from Spinal Cord Injury Using Targeted, Activity-Dependent Intraspinal Stimulation

使用有针对性的活动依赖性椎管内刺激来康复脊髓损伤

• 批准号: 10684699
• 负责人: Steve I Perlmutter
• 金额: $ 53.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10684699
• 关键词: Address; Analgesics; Animals; Anti-Anxiety Agents; Anxiety; Award; Behavioral; Bilateral; COVID-19; COVID-19 pandemic; Cervical; Cervical spinal cord injury; Chronic; Clinical; Clinical Trials; Combined Modality Therapy; Complement; Contusions; Data; Dependence; Development; Effectiveness; Electric Stimulation; Electrodes; Female; Forelimb; Foundations; Funding; Future; Genetic; Goals; Hand; Housing; Intervention; Modeling; Motor; Movement; Muscle; Natural regeneration; Nature; Nervous System; Neural Pathways; Neuronal Plasticity; Neurons; Pain; Pathway interactions; Performance; Persons; Physical Rehabilitation; Physical therapy; Physiological; Psychological Factors; Quality of life; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Research Activity; Sex Differences; Spinal; Spinal cord injury; Stimulus; Stress; Surface; Synaptic plasticity; Technology; Therapy Clinical Trials; Time; Training; Translating; Transplantation; Universities; Vertebral column; Washington; anxiety reduction; arm; brain computer interface; chronic pain; clinical practice; clinical translation; design; effective therapy; environmental enrichment for laboratory animals; experimental study; human subject; improved; laboratory development; learned behavior; male; motor deficit; motor recovery; nervous system disorder; neural circuit; neuroinflammation; neuromechanism; neuronal survival; neuroprosthesis; novel; prevent; response; sex; spinal pathway; synaptogenesis; therapy development; translation to humans

Project Summary The objective of the proposed project is to continue the laboratory’s development of a neuroprosthetic therapy that uses targeted, activity-dependent spinal stimulation to improve arm and hand motor recovery after cervical spinal cord injury (SCI). The project seeks to advance clinical practice through the use of brain-computer-interface technology to harness physiological mechanisms of neural plasticity. Motor deficits severely impact the quality of life of people with SCI, yet current treatments produce limited improvements in movement abilities. Recent clinical and experimental evidence suggests that electrical stimulation of the nervous system can be an effective therapy for a variety of neurological disorders. Here we will extend study of a novel application of electrical stimulation for rehabilitation of forelimb motor deficits in a rat model of cervical SCI. The strategy is designed to enhance the function of spared neural pathways by directing Hebbian plasticity through targeted stimulation of volitionally activated neural circuits. Results will lay the foundation for a future clinical trial using spinal stimulation in human subjects. Previous data demonstrated the effectiveness of multi-channel, intraspinal stimulation triggered by activity of forelimb muscles to improve motor performance in rats with chronic SCI. Specific Aim 1 seeks to complete the characterization of the interplay between stimulation and physical rehabilitation in order to establish principles for combining the therapies. Specific Aim 2 will examine possible causes underlying dramatic differences in recovery in female and male rats treated with the closed-loop stimulation. Specific Aim 3 will determine if activity-dependent epidural stimulation, a much less invasive and easier to translate to clinical practice approach than intraspinal stimulation, is as effective in facilitating recovery.

项目概要 拟议项目的目标是继续实验室的开发 使用有针对性的、活动依赖性脊柱刺激来改善手臂的神经修复疗法 以及颈脊髓损伤（SCI）后手部运动的恢复。该项目旨在推进 通过使用脑机接口技术来利用生理学进行临床实践 神经可塑性机制。 运动缺陷严重影响 SCI 患者的生活质量，但目前的治疗方法 运动能力的提高有限。最近的临床和实验证据 表明神经系统的电刺激可以成为治疗以下疾病的有效方法 各种神经系统疾病。在这里，我们将扩展对电​​气的新颖应用的研究 颈椎 SCI 大鼠模型中前肢运动缺陷的刺激康复。策略 旨在通过指导赫布可塑性来增强幸存神经通路的功能 通过有针对性地刺激意志激活的神经回路。结果将奠定 为未来在人类受试者中使用脊柱刺激的临床试验奠定了基础。 先前的数据证明了多通道椎管内刺激的有效性 由前肢肌肉活动触发，可改善慢性 SCI 大鼠的运动表现。 具体目标 1 旨在完成刺激和刺激之间相互作用的表征。 身体康复，以建立结合疗法的原则。具体目标2 将检查女性和男性康复过程中存在巨大差异的可能原因 用闭环刺激治疗的大鼠。具体目标 3 将确定是否依赖于活动 硬膜外刺激，一种侵入性更小的、更容易转化为临床实践的方法 与脊柱内刺激相比，在促进康复方面同样有效。

项目成果

Neurochip3: An Autonomous Multichannel Bidirectional Brain-Computer Interface for Closed-Loop Activity-Dependent Stimulation.

• DOI: 10.3389/fnins.2021.718465
• 发表时间: 2021
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Shupe LE;Miles FP;Jones G;Yun R;Mishler J;Rembado I;Murphy RL;Perlmutter SI;Fetz EE
• 通讯作者: Fetz EE

Transcriptome of rat subcortical white matter and spinal cord after spinal injury and cortical stimulation.

• DOI: 10.1038/s41597-021-00953-4
• 发表时间: 2021-07-15
• 期刊: Scientific data
• 影响因子: 9.8
• 作者: Kondiles BR;Wei H;Chaboub LS;Horner PJ;Wu JQ;Perlmutter SI
• 通讯作者: Perlmutter SI