Transcranial Electrical Stimulation Promotes Cerebral Blood Flow, Enhancing Cognitive and Motor Recovery with Concurrent Rehab Training after Stroke

经颅电刺激促进脑血流量，通过中风后并发康复训练增强认知和运动恢复

• 批准号: 10609484
• 负责人: Francesca Galeffi
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10609484
• 关键词: Address; Adult; Age; Age Months; Behavioral; Binding; Biological Markers; Blood Vessels; Brain; Calibration; Cause of Death; Cephalic; Cerebrovascular Circulation; Chronic Phase; Clinical Trials; Collateral Circulation; Common carotid artery; Complication; Contralateral; Data Reporting; Disabled Persons; Distal; Dose; Elderly; Electric Stimulation; Female; Frequencies; Genes; Goals; Hour; Human; Impairment; Infarction; Intervention; Ipsilateral; Ischemic Stroke; Knockout Mice; Ligation; Longitudinal Studies; Measures; Mediating; Middle Cerebral Artery Occlusion; Modeling; Monitor; Motor; Mouse Strains; Mus; Nervous System Physiology; Neurologic; Neuronal Plasticity; Neurons; Outcome; Patients; Performance; Perfusion; Peripheral; Persons; Population; Procedures; Proteins; Protocols documentation; Recovery; Recovery of Function; Rehabilitation therapy; Reperfusion Therapy; Risk Factors; Role; Safety; Side; Stroke; Study models; Surrogate Markers; Task Performances; Techniques; Time; Training; Upper Extremity; angiogenesis; cerebrovascular; clinically relevant; cognitive enhancement; cognitive function; cognitive performance; cognitive recovery; comorbidity; density; disability; dosage; experimental study; functional outcomes; gender difference; healthy volunteer; hemodynamics; implementation facilitation; improved; individual variation; long term recovery; male; middle age; military veteran; motor function improvement; motor impairment; motor learning; motor recovery; motor rehabilitation; neurogenesis; neurological recovery; neuronal circuitry; neuronal excitability; neurophysiology; neurovascular; noninvasive brain stimulation; post stroke; prevent; rab GTP-Binding Proteins; rehabilitation strategy; repaired; response; skills; stroke intervention; stroke model; stroke outcome; stroke patient; stroke rehabilitation; thrombolysis; tool; treatment effect; vascular abnormality; young adult

Ischemic stroke is a leading cause of death and serious long-term disability with motor impairment as one of most common complication. Despite significant efforts, effective motor rehabilitation strategies are still lacking. Transcranial alternating current stimulation (tACS) is a promising non- invasive brain stimulation technique that combined with motor task training can facilitates neuroplasticity and motor learning. However, limited understanding of the neurophysiological effects, dose-response relationship, post-stroke motor outcome, safety, and tolerability issue have prevented the successful application of tACS in rehabilitation settings. Individual variation of collateral vessel density it is a critical factor that influence stroke outcome, but likely alters cerebral blood flow (CBF) and activity-dependent plasticity mechanism that support circuit remodeling and motor recovery after stroke. Therefore, we hypothesize that monitoring the interaction between motor rehab training, tACS, and CBF recovery can advance post-stroke rehab intervention. To address the role of the collateral circulation and CBF in recovery, we will assess the ability of tACS (10Hz) to improve motor performance in isogenic strains of mice (males and females at 6 and 12 months of age) and compare it with mice without extensive collateral vasculature. Specific Aim 1: During the four weeks of post-stroke intervention, we will assess the effects of local CBF increase in response to tACS in conjunction with motor rehabilitation training on long-term motor function using local CBF as surrogate maker of neuronal activation and dose-response relationship in WT and collateral-deficient Rabep2-KO mice. Specific Aim 2. To assess the effect of tACS neuronal and vascular plasticity in relationship with stroke outcome We will compare the effects of the motor rehabilitation protocol with and without tACS on post-stroke brain neuroplasticity in relationship to neurological and cognitive function in WT and Rabep2-KO mice. For our model of stroke, we will use a distal middle cerebral artery occlusion (MCAO) plus ipsilateral common carotid artery ligation (CCA) model with reperfusion after 24hr, which is a suitable model for the study of long-term stroke outcomes in young adult and older mice. This, in turn, results in consistent infarct size and significant long-term sensorimotor impairment. Rehab training h to mimic traditional early upper limb motor recovery +/-tACS, (2 dosing groups) will start 72hr after stroke. Long-term recovery mechanisms to be studied include an assessment of motor performance, which will be correlated with post-stroke neurovascular plasticity, neurological and cognitive function. Successful completion of this study will determine treatment effect of TACS on long-term post-stroke motor recovery and utility of CBF as intracranial biomarker for determining effective stimulation protocol.

缺血性中风是导致死亡和严重长期残疾并伴有运动障碍的主要原因 作为最常见的并发症之一。尽管付出了巨大的努力，但有效的运动康复 策略仍然缺乏。经颅交流电刺激（tACS）是一种有前途的非 侵入性脑刺激技术与运动任务训练相结合可以促进 神经可塑性和运动学习。然而，人们对神经生理学的了解有限。 影响、剂量反应关系、中风后运动结果、安全性和耐受性问题 阻碍了 tACS 在康复环境中的成功应用。个体差异 侧支血管密度是影响中风结果的关键因素，但可能会改变大脑 血流（CBF）和活动依赖性可塑性机制支持回路重塑和 中风后运动恢复。因此，我们假设监控之间的相互作用 运动康复训练、tACS 和 CBF 恢复可以促进中风后康复干预。到 为了解决侧支循环和 CBF 在恢复中的作用，我们将评估 tACS (10Hz) 可改善同基因小鼠品系（6 岁时的雄性和雌性）的运动表现 和 12 个月大），并将其与没有广泛侧支脉管系统的小鼠进行比较。具体的 目标1：在中风后干预的四个星期内，我们将评估局部CBF的效果 结合长期运动的运动康复训练，增加对 tACS 的反应 使用局部 CBF 作为神经元激活和剂量反应的替代标记的功能 WT 和侧枝缺陷 Rabep2-KO 小鼠中的关系。具体目标 2. 评估效果 tACS 神经元和血管可塑性与中风结果的关系 我们将比较 使用和不使用 tACS 的运动康复方案对中风后大脑的影响 WT 和 Rabep2-KO 小鼠的神经可塑性与神经和认知功能的关系。 对于我们的中风模型，我们将使用远端大脑中动脉闭塞 (MCAO) 加上 同侧颈总动脉结扎（CCA）模型，24小时后再灌注，这是一种 适合研究年轻成年和老年小鼠长期中风结果的模型。这，在 反过来，导致梗塞面积一致和显着的长期感觉运动障碍。康复中心 将开始模拟传统早期上肢运动恢复+/-tACS（2个剂量组）的训练小时 中风后72小时。有待研究的长期恢复机制包括运动评估 表现，这将与中风后神经血管可塑性、神经系统和 认知功能。这项研究的成功完成将决定 TACS 的治疗效果 长期中风后运动恢复以及 CBF 作为颅内生物标志物的实用性 有效的刺激方案。