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.

项目摘要/摘要 脊髓损伤（SCI）通常是丧失能力的神经损伤 脊柱损坏轴突在大脑和脊髓之间携带感官和运动信号的轴突，以及 转身，身体的其余部分。但是，在对脊髓的挫伤后，至少上面的一些神经元纤维和 病变下方保持完整。最近，我们的实验室和其他人引入了新的神经假体 试图通过利用脑机脊髓界面（BMSIS）来恢复功能的方法。这些 基于设备的系统使用活动依赖性刺激（AD），该刺激（AD）可区分完整的神经活动 运动皮层用作信号，以刺激脊髓病变下方的运动神经元。我们的长期目标 这项研究是脊髓损伤后下肢的运动功能受损的恢复。可行性 在SCI后使用AD作为增强功能恢复的策略的支持 该实验室证明了AD在创伤性脑损伤后恢复熟练运动功能的影响。 因此，这一研究线的总体假设是，广告将导致运动恢复增强 科学后的卧床能力。拟议的项目将通过 广告可以促进大脑皮层和脊髓运动神经元之间增强的通信。 该项目将解决三个特定目的：1）确定脊髓损伤对脊柱的影响 运动神经元活性，皮质脊髓耦合和大鼠的传导时间2）确定最佳尖峰刺激 使用急性中的ADS范式在降级运动途径中提高突触功效的延迟， 麻醉的SCI大鼠模型，3）确定尖峰触发的ISM是否会改善电动机 在科学卧床大鼠模型中的性能。我们将使用急性和慢性神经系统测试这些目标 在麻醉和清醒中记录和刺激技术，表现健康和科幻啮齿动物。这 项目之所以重要，是因为，如果实现，这种方法可能会增强伴随物理和职业 治疗并提高功能能力。最终，患者可能可以恢复自愿运动 提高皮质脊髓纤维中的突触功效。