Inducing Neural Plasticity after Spinal Cord Injury to Recover Impaired Voluntary Movement

脊髓损伤后诱导神经可塑性以恢复受损的随意运动

• 批准号: 9789839
• 负责人: Jordan Alexander Borrell
• 金额: $ 3.31万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789839
• 关键词: Action Potentials; Activities of Daily Living; Acute; Address; Adult; Affect; Aftercare; Animal Model; Area; Axon; Behavior; Behavior assessment; Behavioral; Brain; Bypass; Caring; Cerebral cortex; Chemosensitization; Chronic; Clinical Research; Communication; Contusions; Coupling; Development; Devices; Dimensions; Distant; Electric Stimulation; Fiber; Future; Goals; Hindlimb; Human; Impairment; Implant; Individual; Injury; Laboratories; Lesion; Lower Extremity; Lumbar spinal cord structure; Maps; Medical; Microelectrodes; Modeling; Motor; Motor Cortex; Motor Neurons; Motor Pathways; Movement; Mus; Muscle; Natural regeneration; Neurologic; Neuronal Plasticity; Neurons; Neurostimulation procedures of spinal cord tissue; Occupational Therapy; Paralysed; Patients; Performance; Physical therapy; Population; Pre-Clinical Model; Public Health; Rattus; Recovery of Function; Regenerative Medicine; Research; Rest; Rodent; Role; Sensory; Signal Transduction; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal Cord Lesions; Spinal cord injury; Stem cells; Stimulus; Survivors; Synapses; Synaptic plasticity; System; Techniques; Testing; Time; Trauma; Traumatic Brain Injury; United States; Ventral Horn of the Spinal Cord; Vertebral column; awake; axon injury; base; design; disability; experience; extracellular; functional restoration; improved; insight; intraspinal microstimulation; microstimulation; motor impairment; motor recovery; nerve injury; neurophysiology; neuroprosthesis; novel; novel strategies; novel therapeutics; pre-clinical; preclinical study; relating to nervous system; response; restoration; restorative treatment; young adult

PROJECT SUMMARY/ABSTRACT Spinal cord injury (SCI) is often an incapacitating neural injury most commonly caused by a traumatic blow to the spine, damaging the axons that carry sensory and motor signals between the brain and spinal cord, and in turn, the rest of the body. However, after a contusion to the spinal cord, at least some neuronal fibers above and below the lesion remain intact. Recently, our laboratory and others have introduced new neuroprosthetic approaches in an attempt to restore function by utilizing brain-machine-spinal cord interfaces (BMSIs). These device-based systems use activity-dependent stimulation (ADS) which discriminates neural activity in the intact motor cortex to use as signals to stimulate motor neurons below the spinal cord lesion. Our long-term goal for this research is restoration of impaired motor function in the lower limbs following spinal cord injury. The feasibility of using ADS as a strategy to enhance recovery of function after SCI is supported by the positive results seen in this laboratory demonstrating the effect of ADS in restoring skilled motor function after traumatic brain injury. Thus, the overarching hypothesis of this line of research is that ADS will result in enhanced motor recovery in ambulatory ability after SCI. The proposed project will determine the optimal neurophysiological conditions by which ADS can facilitate enhanced communication between the cerebral cortex and spinal cord motor neurons. The project will address three specific aims: 1) Determine the effects of a contusive spinal cord injury on spinal motor neuron activity, corticospinal coupling, and conduction time in rats 2) determine the optimal spike-stimulus delay for increasing synaptic efficacy in descending motor pathways using an ADS paradigm in an acute, anesthetized rat model of SCI, and 3) determine whether spike-triggered ISMS results in improved motor performance in an ambulatory rat model of SCI. We will test these aims using acute and chronic neurologic recording and stimulating techniques in both anesthetized and awake, behaving healthy and SCI rodents. The project is significant because, if realized, this approach may augment concomitant physical and occupational therapy and result in improved functional abilities. Ultimately, patients may could regain voluntary movement due to increased synaptic efficacy in corticospinal fibers.

项目概要/摘要 脊髓损伤 (SCI) 通常是一种导致丧失能力的神经损伤，最常见的原因是外伤性打击 脊柱，损害在大脑和脊髓之间传递感觉和运动信号的轴突， 转动，身体的其余部分。然而，脊髓挫伤后，至少上面和下面的一些神经元纤维会受到损伤。 病灶下方保持完整。最近，我们实验室等推出了新型神经假体 尝试利用脑-机-脊髓接口（BMSI）恢复功能。这些 基于设备的系统使用活动依赖性刺激（ADS）来区分完整的神经活动 运动皮层用作信号刺激脊髓病变下方的运动神经元。我们的长期目标是 这项研究旨在恢复脊髓损伤后下肢受损的运动功能。可行性 使用 ADS 作为促进 SCI 后功能恢复的策略得到了以下积极结果的支持： 该实验室展示了 ADS 在恢复脑外伤后熟练运动功能方面的作用。 因此，这一系列研究的总体假设是 ADS 将导致增强的运动恢复 SCI 后的行走能力。拟议的项目将通过以下方式确定最佳的神经生理条件： 其中ADS可以促进增强大脑皮层和脊髓运动神经元之间的通讯。 该项目将实现三个具体目标：1）确定挫伤性脊髓损伤对脊柱的影响 大鼠运动神经元活动、皮质脊髓耦合和传导时间 2) 确定最佳尖峰刺激 使用 ADS 范式在急性、 SCI 麻醉大鼠模型，以及 3) 确定尖峰触发的 ISMS 是否会改善运动能力 SCI 动态大鼠模型中的表现。我们将使用急性和慢性神经病学来测试这些目标 对麻醉和清醒、行为健康和 SCI 啮齿动物进行记录和刺激技术。这 该项目意义重大，因为如果实现的话，这种方法可能会增强伴随的身体和职业 治疗并改善功能能力。最终，患者可能会因恢复自主运动而恢复自主运动。 增加皮质脊髓纤维的突触功效。