Vagus Nerve Stimulation Paired with Rehabilitative Training to Enhance Plasticity

迷走神经刺激与康复训练相结合以增强可塑性

• 批准号: 9054938
• 负责人: MICHAEL P KILGARD
• 金额: $ 38.54万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9054938
• 关键词: Activities of Daily Living; Affect; Axon; Behavioral; Case Study; Categories; Clinical; Development; Effectiveness; Elderly; Electrophysiology (science); Exhibits; Forelimb; Goals; Guidelines; Health; Impairment; Industry; Ischemic Brain Injury; Ischemic Stroke; Maps; Modeling; Motor; Motor Cortex; Movement; Neuronal Plasticity; Neurons; Outcome; Patients; Physical Rehabilitation; Population; Rattus; Recovery; Recovery of Function; Red nucleus structure; Rehabilitation therapy; Risk Factors; Speed; Spinal Cord; Staging; Stroke; Target Populations; Techniques; Testing; Training; Translations; United States; Upper Extremity; age related; aged; aging population; cortex mapping; disability; high risk; improved; insight; ischemic lesion; motor function recovery; motor recovery; novel; preclinical study; research study; stroke recovery; stroke therapy; vagus nerve stimulation; young adult

DESCRIPTION (provided by applicant): Stroke is a leading cause of disability, with an estimated 795,000 cases reported in the US each year. As many as 70% of patients who suffer a stroke display a long-term impairment in upper extremity motor function. Many stroke patients exhibit associated risk factors which can impair recovery of function, such as advanced age. The development of rehabilitative strategies to improve the recovery of motor function in the context of advanced age is of key importance. We propose to evaluate a novel early stage therapy to improve stroke recovery which utilizes stimulation of the vagus nerve paired with rehabilitative training. Pairing vagus nerve stimulation (VNS) with movement results in highly specific, long-lasting neuroplasticity in rat primary motor cortex. Furthermore, VNS delivered during rehabilitation improves recovery of forelimb speed and strength after an ischemic lesion of the motor cortex in young adult rats. To evaluate if VNS paired with physical rehabilitation may be useful in stroke patients, we propose to test the therapy in a model that more accurately represents the clinical population. Because advanced age is a leading risk factor for stroke and may limit plasticity, the experiments described in this proposal will evaluate VNS in a model of stroke at an advanced age. The first aim of the study will assess the ability of VNS paired with rehabilitative training to improve recovery of motor function after ischemic stroke in aged rats. The second aim of this proposal will examine structural plasticity mechanisms that underlie recovery after stroke. The third aim of the study will assess the ability of VNS paired with physical training to enhance map plasticity in motor cortex of aged rats. We hypothesize that in aged rats, VNS paired with physical training will result in improved recovery of function, increased structural plasticity, and enhanced map plasticity beyond physical training alone. The results of the proposed experiments will clarify the relationship between advanced age and recovery of motor function are stroke. Insights from these studies will help to delineate the clinical population for which VNS paired with physical rehabilitation is likely to confer therapeutc benefits and improve the likelihood of successful translation of the therapy.

描述（由申请人提供）：中风是导致残疾的主要原因，估计每年在美国报告795，000例。多达70%的中风患者显示上肢运动功能的长期损伤。许多中风患者表现出可能损害功能恢复的相关风险因素，例如高龄。制定康复策略以改善老年人运动功能的恢复至关重要。我们建议评估一种新的早期治疗，以改善中风恢复，利用刺激迷走神经配对康复训练。配对迷走神经刺激（VNS）与运动的结果在大鼠初级运动皮层高度特异性，持久的神经可塑性。此外，在康复期间提供的VNS改善了年轻成年大鼠运动皮层缺血性损伤后前肢速度和力量的恢复。为了评估迷走神经刺激与物理康复相结合是否对中风患者有用，我们建议在一个更准确地代表临床人群的模型中测试该疗法。由于高龄是中风的主要危险因素，可能会限制可塑性，本提案中描述的实验将评估高龄中风模型中的VNS。本研究的第一个目的是评估迷走神经刺激结合康复训练改善老年大鼠缺血性卒中后运动功能恢复的能力。第二个目标是研究中风后恢复的结构可塑性机制。本研究的第三个目的是评估运动神经刺激结合运动训练对老年大鼠运动皮层地图可塑性的影响。我们假设，在老年大鼠，VNS与体育训练配对将导致改善功能恢复，增加结构可塑性，并增强地图可塑性超过单独的体育训练。本实验结果将阐明高龄与脑卒中运动功能恢复之间的关系。从这些研究的见解将有助于划定的临床人群，VNS与物理康复配对可能会赋予therapeutic的好处，并提高成功翻译的治疗的可能性。