Priming the Rehabilitation Engine: Aerobic Exercise as the Fuel to Spark Behavioral Improvements in Stroke

启动康复引擎：有氧运动作为改善中风行为的燃料

• 批准号: 10400049
• 负责人: Ryan Ross
• 金额: --
• 依托单位: RALPH H JOHNSON VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10400049
• 关键词: Address; Adjuvant; Admission activity; Aerobic Exercise; Award; Behavioral; Biological Markers; Blood specimen; Brain; Brain-Derived Neurotrophic Factor; Cognition; Cognitive; Coupled; Data; Development; Ducks; Effectiveness; Environment; Exercise; Exposure to; Fostering; Foundations; Funding; Future; Goals; Health; Impairment; Individual; Infrastructure; Institution; Intervention; Long-Term Potentiation; Lower Extremity; Measures; Medical; Medical center; Mental Depression; Mentors; Motor; Movement; Neurobiology; Neurologic; Neuronal Plasticity; Outcome; Participant; Patient Self-Report; Physical Function; Physical Performance; Physical Rehabilitation; Physical assessment; Play; Positioning Attribute; Prevalence; Process; Psyche structure; Quality of life; Randomized; Rehabilitation therapy; Research; Research Personnel; Resources; Role; South Carolina; Stretching; Stroke; Synapses; Therapeutic Intervention; Training; Transcranial magnetic stimulation; Treatment Efficacy; United States; United States National Institutes of Health; Universities; Upper Extremity; Veterans; Work; arm function; base; cardiovascular health; chronic stroke; cognitive function; cohort; data acquisition; depressive symptoms; design; disability; effective intervention; executive function; experience; functional improvement; improved; improved functioning; innovation; insight; mental function; mortality; motor learning; motor rehabilitation; multidisciplinary; neurological rehabilitation; neuropsychiatry; post stroke; predicting response; psychologic; rehabilitation paradigm; rehabilitation research; rehabilitation strategy; rehabilitative care; response; skills; stroke outcome; stroke recovery; stroke rehabilitation; stroke survivor; tool; virtual reality

Stroke is a leading cause of disability in the United States and poses a significant burden to Veterans. The effectiveness of current intervention approaches is limited and many individuals following stroke live with persistent functional, cognitive and psychological impairments that significantly reduce long-term quality of life. The prevalence of post-stroke disability coupled with reduced stroke mortality rates reflects an increasing need to develop effective rehabilitation strategies aimed at reducing disability and improving quality of life for Veteran stroke survivors. Aerobic exercise (AEx) promotes numerous functional, cognitive, and psychological benefits. Additionally, AEx may enhance neuroplasticity through increases in circulating brain-derived neurotrophic factor (BDNF) and corticomotor excitability (CME). Emerging evidence also supports the use of AEx as a priming tool to enhance motor outcomes following targeted rehabilitation. Our conceptual framework involves priming with AEx prior to targeted motor rehabilitation to enhance the ‘neuroplastic environment” and make the brain more amenable to adaptation, thereby enhancing response to rehabilitation. Specifically, we propose to pair AEx with an upper extremity virtual reality rehabilitation game called Duck Duck Punch (DDP), developed by our team (Co-mentor: Woodbury) as the platform for examining the adjunctive potential of AEx. Therefore the primary aim of this proposal is to evaluate the priming effects of AEx on a motor rehabilitation intervention (i.e. DDP) for chronic stroke survivors. This will be accomplished by examining a cohort of stroke survivors who will be randomly assigned to receive 8 weeks (3 sessions/week) of DDP preceded by either 15 minutes of AEx (AEx+DDP) or a stretching control (CON+DDP). Assessment of physical function before and after the intervention will provide insight into the ability of AEx to enhance the response to motor rehabilitation. The secondary aim of this proposal is to gain insight into the mechanisms that underlie the priming effects of AEx through assessment of circulating BDNF and CME. Additionally, since stroke survivors often experience cognitive and psychological impairments we will also explore the influence of cognitive and psychological function on response to AEx+DDP. A potentially exciting possibility is that AEx facilitates an enhanced neuroplastic environment, which fosters improved function in a variety of aspects of stroke recovery including physical, cognitive, and psychological function. This proposal will be supported by the infrastructure and resources provided by the South Carolina Research Center for Recovery from Stroke (NIH P20 GM109040). Furthermore, the combination of the Ralph H. Johnson VA Medical Center and its affiliated academic institution, Medical University of South Carolina is uniquely positioned to fill the aforementioned gap in understanding for several reasons: 1) Charleston, South Carolina has one of the highest rates of stroke in the nation, and 2) in the last 5 years we have received over $23 million in research funds to support rehabilitation research in stroke recovery. During the award period, the applicant will capitalize on the opportunity to utilize these resources to develop the requisite skills and understanding of neurobiological data acquisition, analysis, and interpretation through direct hands-on training from local renowned experts. The overall goal of this CDA-2 application is to expose the candidate to a rich local environment for stroke recovery research, providing the foundation for his development into an independent VA researcher studying the effects of exercise- based interventions, alone or as adjuvants, for the treatment of Veterans. To accomplish this goal, the proposed training plan will enhance the candidate’s understanding of the neurobiological effects of AEx and the design and delivery of neurorehabilitation trials. The data generated will inform the development of additional AEx-based interventions aimed at improving function and quality of life for individuals following stroke and perhaps other neurological or neuropsychiatric conditions.

在美国，中风是导致残疾的主要原因，给退伍军人带来了巨大的负担。这个 目前干预方法的有效性是有限的，许多中风患者生活在 持续性的功能、认知和心理障碍，显著降低长期生活质量。 中风后残疾的流行，加上中风死亡率的降低，反映了日益增长的需求 制定有效的康复策略，旨在减少退伍军人的残疾和提高生活质量 中风幸存者。有氧运动(AEX)可以促进许多功能、认知和心理方面的益处。 此外，AEX可能通过增加循环中脑源性神经营养因子来增强神经可塑性 (BDNF)和皮质运动兴奋性(CME)。新出现的证据也支持使用AEX作为启动工具 以提高有针对性的康复后的运动效果。我们的概念框架涉及到 AEX之前有针对性的运动康复，以增强‘神经可塑性环境’，并使大脑更 适应能力强，从而加强对康复的反应。具体地说，我们建议将AEX与 一款由我们团队开发的上肢虚拟现实康复游戏Duck Duck Punch(DDP (共同导师：伍德伯里)作为考察AEX附加潜力的平台。因此，主要的 本建议的目的是评估AEX在运动康复干预中的启动效果。 DDP)用于慢性中风幸存者。这将通过检查中风幸存者的队列来实现 将随机分配到接受8周(3次/周)的DDP，并在此之前接受15分钟的AEX (AEX+DDP)或拉伸控制(CON+DDP)。治疗前后的身体功能评定 干预将提供对AEX增强运动康复反应的能力的洞察。这个 这项建议的次要目的是深入了解AEX启动效应的基础机制 通过对循环BDNF和CME的评估。此外，由于中风幸存者经常经历 我们还将探讨认知和心理障碍对认知和心理的影响 作用于对AEX+DDP的反应。一个潜在的令人兴奋的可能性是，AEX促进了增强的 神经整形环境，在中风康复的各个方面促进改善功能，包括 生理、认知和心理功能。这项提议将得到基础设施和 由南卡罗来纳州中风康复研究中心提供的资源(NIH P20 GM109040)。 此外，拉尔夫·H·约翰逊退伍军人医学中心及其附属学术机构的结合， 南卡罗来纳医科大学在填补上述认识空白方面具有独特的地位 有几个原因：1)南卡罗来纳州的查尔斯顿是全国中风发病率最高的城市之一，2)在美国 在过去的5年里，我们已经收到了超过2300万美元的研究资金，用于支持中风的康复研究 恢复。在授权期内，申请者将利用这些资源的机会 培养获取、分析和解释神经生物学数据所需的技能和理解 通过当地知名专家的直接动手培训。此CDA-2应用程序的总体目标是 将候选人暴露在丰富的本地环境中进行中风恢复研究，提供 为他发展成为研究运动效果的独立退伍军人管理局研究员奠定了基础- 为治疗退伍军人单独或作为辅助的基于干预措施。为了实现这一目标， 建议的培训计划将加强候选人对AEX的神经生物学效应和 设计和实施神经康复试验。生成的数据将为开发其他 旨在改善卒中患者功能和生活质量的基于AEX的干预措施 也许是其他神经或神经精神疾病。