Heart-Brain Retraining: Forced Aerobic exercise for Stroke Rehabilitation

心脑再训练：中风康复的强制有氧运动

• 批准号: 8359195
• 负责人: JAY L. ALBERTS
• 金额: $ 7.42万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359195
• 关键词: Acute; Aerobic; Aerobic Exercise; American; Animals; Antiparkinson Agents; Automobile Driving; Beck depression inventory; Biomechanics; Brain; Brain-Derived Neurotrophic Factor; Cardiovascular Diseases; Cardiovascular system; Chronic; Clinical; Cognition; Coupled; Data; Development; Disabled Persons; Dose; Exercise; Exhibits; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Global Change; Goals; Health; Heart; Human; Image; Intervention; Life; Literature; Lower Extremity; Methods; Motor; Nervous System Physiology; Neuraxis; Neurologic Deficit; Neuronal Plasticity; Neurorehabilitation; Outcome; Parkinson Disease; Patients; Pattern; Pharmaceutical Preparations; Randomized; Recovery; Recovery of Function; Recurrence; Rehabilitation therapy; Reporting; Residual state; Rodent; Smell Perception; Stroke; Survivors; Testing; Time; Trail Making Test; Training; United States; United States National Institutes of Health; Upper Extremity; Walking; Wolves; base; blind; cardiovascular risk factor; cognitive function; constraint induced movement therapy; cost; cost effective; disability; fitness; hemiparesis; improved; neuroprotection; neurotrophic factor; post stroke; prevent; primary outcome; relating to nervous system; repetitive task practice; response; secondary outcome; stroke recovery; stroke rehabilitation

DESCRIPTION (provided by applicant): The goal of this study is to gather initial data regarding the potential of forced aerobic exercise to augment recovery of function in patients with stroke. Stroke, an endpoint of cardiovascular disease, is the leading cause of disability in the United States, and an estimated 5.8 million Americans are living with residual neurologic deficit due to stroke. Current approaches to stroke rehabilitation involve intensive, therapist-directed task practice that is both expensive and, in some cases, ineffective in fostering functional neuromotor recovery. The identification of a safe, cost-effective approach, such as forced aerobic exercise, to augment the recovery of function post-stroke would reduce the cost associated with intensive rehabilitation while simultaneously decreasing the cardiovascular risk factors prevalent in stroke survivors. Animal and human literature reveal that acute bouts of high-rate aerobic exercise results in increased concentrations of neurotrophic factors including brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF). These neurotrophic factors have been implicated as the mechanism that promotes neuroprotection, neurorecovery, and neuroplasticity. Clinical improvements in motor and cognitive function have been reported as a result of intensive aerobic exercise training, hypothesized to be due to this endogenous release of neurotrophins. These global changes in neurologic function have not been reported in patients with stroke. The PIs hypothesize that the pathophysiology of stroke, which limits sustained high rate and high intensity exercise, prevents the endogenous release of these neurotrophic factors. The PIs developed a safe lower extremity forced exercise intervention in Parkinson's disease (PD) patients that allows them to achieve an exercise rate greater than their voluntary rate. Following an eight week forced exercise intervention, PD patients exhibit significant improvements in global motor functioning, fine motor upper extremity function, cognition and olfaction. Based on fMRI data, acute forced exercise in PD patients indicates a similar pattern of cortical and subcortical activation between forced exercise and antiparkinsonian medication, suggesting forced-exercise does alter brain function. To investigate the effects of aerobic exercise on the recovery of function in stroke patients, a two year, single-center, parallel-group, rater-blind preliminary study is proposed. A total of 30 chronic (6-12 months post) stroke patients with residual hemiparesis will be randomized to one of three groups: combined forced-exercise and repetitive task practice (FE+RTP), combined voluntary exercise and repetitive task practice (VE+RTP) or a dose-matched RTP only (RTP only) group. All three groups will receive an identical dose of rehabilitation time over a course o 8 weeks (3X per week); however, the combination groups will perform forced or voluntary exercise for 50% of the session and RTP for the remaining 50% of the session. The RTP only group will engage in RTP exclusively. Outcomes will be gathered at baseline, mid-treatment and end of treatment (EOT). It is hypothesized that the forced-exercise intervention will serve to prime the central nervous system resulting in improved clinical outcomes for the FE+RTP group. Comparable improvements in aerobic capacity are expected for both exercise groups. If forced exercise is shown effective, it could become a viable adjunct to current neurorehabilitation approaches in driving neural recovery while simultaneously improving cardiovascular health. PUBLIC HEALTH RELEVANCE: Current approaches to stroke rehabilitation involve intensive, therapist-directed task practice that is expensive and in some cases ineffective in fostering functional neuromotor recovery. The identification of a safe, cost-effective approach, such as forced aerobic exercise, to augment the recovery of function post-stroke would reduce the cost associated with intensive rehabilitation while simultaneously decreasing the cardiovascular risk factors prevalent in stroke survivors. The PIs have developed a safe lower-extremity forced exercise intervention for patients with Parkinson's disease that has been shown to improve global motor function, cognition and olfaction. These changes coupled with functional magnetic resonance imaging patterns suggest that forced-exercise may be altering brain function. The PIs are proposing to conduct a preliminary study to investigate the effects of forced versus voluntary-rate aerobic exercise on the recovery of neurologic function in patients with stroke. Identifying the relationship between aerobic exercise (forced or voluntary) and the recovery of motor and non-motor function post-stroke will serve to optimize current neurorehabilitation approaches.

描述（由申请人提供）：本研究的目的是收集关于强制有氧运动增强脑卒中患者功能恢复潜力的初步数据。中风是心血管疾病的终点，是美国致残的主要原因，估计有580万美国人生活在中风引起的残余神经功能缺陷中。目前中风康复的方法包括密集的、由治疗师指导的任务实践，这既昂贵，在某些情况下，对促进功能性神经运动恢复无效。确定一种安全、具有成本效益的方法，如强制有氧运动，以增强中风后的功能恢复，将降低与强化康复相关的成本，同时降低卒中幸存者中普遍存在的心血管危险因素。动物和人类文献显示，急性高速率有氧运动可导致脑源性神经营养因子（BDNF）和胶质源性神经营养因子（GDNF）浓度增加。这些神经营养因子被认为是促进神经保护、神经恢复和神经可塑性的机制。据报道，运动和认知功能的临床改善是高强度有氧运动训练的结果，假设是由于内源性神经营养因子的释放。这些神经功能的整体变化尚未在中风患者中报道。PIs假设中风的病理生理限制了持续的高速率和高强度的运动，阻止了这些神经营养因子的内源性释放。pi为帕金森病（PD）患者开发了一种安全的下肢强制运动干预，使他们能够实现比自愿率更高的运动率。经过8周的强制运动干预，PD患者在整体运动功能、上肢精细运动功能、认知和嗅觉方面表现出显著改善。基于功能磁共振成像（fMRI）数据，PD患者的急性强迫运动表明，在强迫运动和抗帕金森药物治疗之间，皮层和皮层下的激活模式相似，这表明强迫运动确实改变了大脑功能。为了研究有氧运动对脑卒中患者功能恢复的影响，提出了一项为期两年的单中心、平行组、非盲的初步研究。共有30例慢性（6-12个月后）卒中残余偏瘫患者将被随机分为三组：联合强制运动和重复任务练习（FE+RTP），联合自愿运动和重复任务练习（VE+RTP）或剂量匹配的RTP组（RTP）。所有三组将在8周的疗程中接受相同剂量的康复时间（每周3次）；然而，组合组将在50%的会话中进行强制或自愿锻炼，并在其余50%的会话中进行RTP。RTP专属组将专门参与RTP。结果将在基线、治疗中期和治疗结束（EOT）收集。假设强迫运动干预将有助于激活中枢神经系统，从而改善FE+RTP组的临床结果。预期两组的有氧能力都有类似的改善。如果强制运动被证明是有效的，它可能成为当前神经康复方法的可行辅助手段，在促进神经恢复的同时改善心血管健康。