Ischemic Conditioning and Improved Motor Function Post Stroke

项目摘要 中风后，神经系统无法完全激活肌肉组织，从而导致心血管疾病。 去适应这些损伤限制了行走等任务，并导致长期残疾。目的 这项研究的目的是检查一种称为缺血性条件反射（IC）的非侵入性干预是否可以改善步态 速度，麻痹腿部肌肉组织的神经激活和心血管健康， 跑步机训练简而言之，IC是一种非侵入性刺激，其通过使用血压袖带触发，以短暂地测量血压。 在5分钟内阻断流向目标组织（麻痹腿）的血流，每次共进行5个循环， 使组织暂时缺血在没有中风的个体中，已知IC刺激会增加 运动系统的兴奋性和改善血液的局部调节，但IC对运动任务的积极影响 例如中风患者的行走是未知的。我们建议研究IC对步行的影响 速度和麻痹腿功能，具有三个特定目标。在目标1中，我们将展示结合 IC和跑步机训练对中风后步行速度的影响。我们将采用前瞻性随机对照设计 对三组慢性中风患者（每组25人）进行为期四周（共12次）的训练： IC+跑步机训练，IC Sham+跑步机训练和仅IC。将在基线时测量行走速度， 1次治疗后、6次治疗后、12次治疗后和干预后1个月。我们预计， 在12次训练后，中风IC+跑步机训练组的步行速度。在目标2中，我们将量化 IC和跑步机训练对改善轻瘫肌肉激活和疲劳性的作用。由于增强的神经 激活肌肉，我们预计，IC对麻痹腿将改善力量和神经肌肉 疲劳性最大膝伸肌扭矩生成（强度）和维持次最大 将在目标1中描述的所有治疗组中评估力（疲劳性）。我们预计， 在12个疗程后，中风IC+跑步机组的力量和任务持续时间发生了变化。在目标3中，我们 将确定IC+跑步机训练改善内皮功能和心肺功能。我们 假设IC+跑步机训练将导致腘动脉的血流介导扩张增加， 麻痹腿和非麻痹臂的肱动脉。沿着肌肉激活的改善， 预测中风IC +跑步机训练组将有增加的有氧能力， 运动试验测量峰值摄氧量（VO2 Peak）。这些研究将首次量化 IC是一种非侵入性、易于管理、具有成本效益的干预措施，对步行速度、运动功能和 慢性中风患者的心肺适能这项研究的结果有可能对 通过证明IC作为步行功能辅助治疗的有效性， 中风未来的研究将探讨IC的分子机制，IC对急性脑卒中的影响， 人群，以及IC与其他步行者相比的疗效。

Project Summary After stroke, the nervous system is unable to fully activate the musculature, which leads to cardiovascular deconditioning. These impairments limit tasks such as walking and contribute to long term disability. The purpose of this study is to examine if a non-invasive intervention, called ischemic conditioning (IC), can improve gait speed, neural activation of the paretic leg musculature, and cardiovascular fitness when combined with traditional treadmill training. Briefly, IC is a non-invasive stimulus which is triggered by using a blood pressure cuff to briefly occlude blood flow to the tissue of interest (the paretic leg) in 5-minute bouts, done a total of 5 cycles per session, making the tissue transiently ischemic. In individuals without stroke, the IC stimulus is known to increase the excitability of motor systems and improve local regulation of blood, but the positive effects of IC on motor tasks such as walking in individuals with stroke are unknown. We propose to investigate the effects of IC on walking speed and paretic leg function with three Specific Aims. In Aim 1, we will demonstrate the benefit of combined IC and treadmill training on walking speed post stroke. We will use a prospective randomized control design with three groups of individuals with chronic stroke (25 per group) for four weeks (12 total sessions) of training: IC+Treadmill Training, IC Sham+Treadmill Training, and IC only. Walking speed will be measured at baseline, after 1 session, 6 sessions, 12 sessions, and 1 month post intervention. We anticipate the largest gains in walking speed in the stroke IC+Treadmill Training group after 12 sessions. In Aim 2, we will quantify the effects of IC and treadmill training on improvements in paretic muscle activation and fatigability. Due to enhanced neural activation of the muscle, we anticipate that IC on the paretic leg will improve strength and neuromuscular fatigability. Maximal knee extensor torque generation(strength) and ability to sustain a sub-maximal force(fatigability) will be assessed in all treatment groups described in Aim 1. We expect that the largest gains in strength and task duration to occur in the stroke IC+Treadmill group after 12 sessions. Finally, in Aim 3, we will establish that IC+Treadmill Training improves endothelial function and cardiorespiratory fitness. We hypothesize that IC+Treadmill Training will result in increased flow mediated dilation in the popliteal artery of the paretic leg and the brachial artery of the non-paretic arm. Along with improvements in muscle activation, we predict the stroke IC + Treadmill training group will have an increased aerobic capacity as assessed by a graded exercise test to measure peak oxygen uptake (VO2 Peak). These studies will be the first to quantify the effects of IC, a non-invasive, easy to administer, cost-effective intervention, on walking speed, motor function and cardiorespiratory fitness in chronic stroke. The findings from this study have the potential to greatly impact neurorehabilitation strategies by demonstrating the effectiveness of IC as an adjunct on walking function post stroke. Future studies will investigate the molecular mechanisms of IC, the effects of IC on acute stroke populations, and the efficacy of IC compared with other walking adjuncts.