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

缺血性中风是导致死亡和严重的长期残疾并伴有运动障碍的主要原因。 是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 战略仍然缺乏。经颅交流电刺激(TACS)是一种很有前途的非电刺激疗法。 结合运动任务训练的侵入性脑刺激技术可以促进 神经可塑性和运动学习。然而，对神经生理学的了解有限 影响、剂量-反应关系、卒中后运动结局、安全性和耐受性问题 妨碍了TAC在康复环境中的成功应用。的个体差异 侧支血管密度是影响卒中预后的关键因素，但可能改变大脑 血流(CBF)和活动依赖的可塑性机制，支持电路重构和 中风后的运动恢复。因此，我们假设监测之间的相互作用 运动康复训练、TACS和CBF恢复可促进卒中后康复干预。至 解决侧支循环和CBF在复苏中的作用，我们将评估 TAC(10赫兹)，以改善同基因品系小鼠的运动能力(雄性和雌性在6 和12个月龄)，并与没有广泛侧支血管的小鼠进行比较。特定的 目的1：在卒中后四周的干预中，我们将评估局部脑血流的影响 在长期运动康复训练的同时增加对TACS的反应 局部脑血流量作为神经元激活和剂量反应替代指标的功能 WT与侧支缺陷Rabp2-KO小鼠的关系。具体目标2.评估效果 Tacs神经元和血管可塑性与卒中预后的关系我们将比较 运动康复方案加与不加TACS对卒中后脑的影响 WT和RABEP2-KO小鼠神经可塑性与神经和认知功能的关系。 对于我们的卒中模型，我们将使用大脑中动脉远端闭塞(MCAO)加 同侧颈总动脉结扎(CCA)24小时后再通的动物模型 适合青壮年和老年小鼠中风长期结局研究的模型。这个，在 反过来，导致一致的梗死面积和显著的长期感觉运动障碍。康复中心 模拟传统早期上肢运动恢复的训练h将开始+/-Tacs，(2个剂量组) 卒中后72小时。需要研究的长期恢复机制包括对马达的评估 表现，这将与中风后神经血管可塑性，神经学和 认知功能。这项研究的成功完成将确定Tacs对糖尿病的治疗效果。 卒中后远期运动功能恢复及脑血流量作为颅内生物标志物的应用 有效的刺激方案。

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.