Enhancing Sympathetic Outflow Control Following Spinal Cord Injury Using Targeted Plasticity Therapy

使用靶向可塑性疗法增强脊髓损伤后的交感神经流出控制

基本信息

批准号：
10637220
负责人：
Patrick D Ganzer
金额：
$ 49.36万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10637220
关键词：
Address Affect Animals Area Baroreflex Behavior Blood Blood flow Cardiovascular Physiology Cardiovascular system Cell Nucleus Cervical spinal cord injury Data Dedications Electrophysiology (science)Event Forelimb Functional disorder Goals Health Human Hypothalamic structure Investigation Lateral Maps Measures Mission Modeling Motor Movement Muscle Muscle Fatigue Muscle function Nervous System Trauma Neural Pathways Neuroanatomy Neuromodulator Neuronal Plasticity Organ Paralysed Pathway interactions Patients Perfusion Peripheral Physiology Prosencephalon Public Health Rattus Recovery Rehabilitation therapy Research Resistance Spinal Cord Spinal cord injury Stroke Synapses System Techniques Technology Testing Therapeutic Time Tissues Training Travel United States Food and Drug Administration United States National Institutes of Health Upper Extremity Upper limb movement Work cholinergic effective therapy exercise intolerance experience experimental group experimental study improved mad itch virus microstimulation motor control multidisciplinary neural circuit neuroregulation neurotransmitter release novel therapeutics simulation translational potential vagus nerve stimulation

项目摘要

Abstract Almost all sympathetic outflow control pathways travel through the spinal cord for affecting the peripheral tissues. Cervical spinal cord injury impacts sympathetic outflow control, leading to several debilitating deficits (in addition to paralysis), including an inability to redistribute blood to active tissues and muscle fatigue. There are currently no consistently effective treatments for sympathetic outflow control dysfunction following cervical spinal cord injury. The long-term goal of this research is to address this significant gap using vagus nerve stimulation paired with rehabilitation to enhance sympathetic outflow control following cervical spinal cord injury. Pairing vagus nerve stimulation with movements during rehabilitation leads to the rapid release of plasticity enhancing neuromodulators, leading to the reorganization of motor control systems. The objective of this proposal is to determine the specific effects of vagus nerve stimulation paired with rehabilitation on sympathetic outflow control following cSCI, and determine the neural pathways contributing to these effects. We will also assess the optimal delivery regime for vagus nerve stimulation (with or without rehabilitation). Our central hypothesis is that vagus nerve stimulation precisely paired with movements during rehabilitation enhances the plasticity of spared sympathetic outflow control circuits, leading to improved motor endurance and muscle fatigue resistance following cSCI. We will assess this hypothesis via three specific aims: 1) determine the effects of vagus nerve stimulation paired with rehabilitation on forelimb muscle and cardiovascular function; and measure changes in 2) cortical and 3) subcortical plasticity related to sympathetic outflow control. We will pursue these aims using multidisciplinary assessments, leveraging electrophysiological and neuroanatomical techniques. The proposed research is significant, as it will determine if vagus nerve stimulation paired with rehabilitation is a viable therapy for treating sympathetic control dysfunction following cervical spinal cord injury. Furthermore, these results will elucidate the critical relationships between forelimb function, sympathetic outflow control, vagus nerve stimulation therapy, and neuroplasticity.

抽象的几乎所有交感神经流出控制途径都通过脊髓传播，以影响周围组织。宫颈脊髓损伤会影响交感神经的流出控制，导致几个令人衰弱的缺陷（此外瘫痪），包括无法将血液重新分配至活性组织和肌肉疲劳。目前有在脊髓脊髓后，没有一贯的有效的交感神经流出控制功能障碍受伤。这项研究的长期目标是使用迷走神经刺激配对来解决这一显着差距通过康复，可以增强宫颈脊髓损伤后的交感神经流出控制。配对迷走神康复过程中随动作的神经刺激导致可塑性的快速释放增强神经调节剂，导致运动控制系统的重组。该提议的目的是确定迷走神经刺激与康复对交感神经流出控制的特定影响遵循CSCI，并确定导致这些影响的神经途径。我们还将评估最佳迷走神经刺激（有或没有康复）的递送制度。我们的中心假设是迷走神经神经刺激在康复过程中精确与动作配对，可以增强保险的可塑性交感神经的流出控制电路，从而改善运动耐力和肌肉疲劳阻力遵循CSCI。我们将通过三个特定目的评估这一假设：1）确定迷走神经的影响刺激与前肢肌肉和心血管功能的康复配对；并衡量变化 2）皮质和3）与交感神经流出控制有关的皮层可塑性。我们将使用这些目标多学科评估，利用电生理和神经解剖技术。提议研究很重要，因为它将确定迷走神经刺激是否与康复配对是一种可行的治疗用于治疗宫颈脊髓损伤后的交感神经控制功能障碍。此外，这些结果将阐明前肢功能，交感神经流控制，迷走神经之间的临界关系刺激疗法和神经可塑性。