Ischemic Conditioning and Improved Motor Function Post Stroke

项目摘要 中风后，神经系统不能完全激活肌肉系统，从而导致心血管疾病 解除条件。这些障碍限制了行走等任务，并导致长期残疾。目的 这项研究的目的是检验一种名为缺血适应(IC)的非侵入性干预是否可以改善步态 速度、瘫痪腿部肌肉的神经激活，以及当与传统的 跑步机训练。简单地说，IC是一种非侵入性刺激，通过使用血压袖带短暂地触发 在5分钟的比赛中阻断流向感兴趣组织(瘫痪腿)的血流，每次总共进行5个循环， 使组织瞬间发生缺血。在没有中风的人中，IC刺激已知会增加 运动系统的兴奋性和改善局部血液调节，但IC对运动任务的积极影响 比如行走在中风患者身上就不得而知了。我们建议研究IC对步行的影响 速度和瘫痪腿的功能有三个具体的目标。在目标1中，我们将演示组合的好处 IC和跑步机训练对中风后步行速度的影响。我们将使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节)的训练： IC跑步机训练、IC Sham跑步机训练和IC Only。步行速度将在基线上测量， 干预后1个疗程、6个疗程、12个疗程、1个月。我们预计年内涨幅最大 卒中IC跑步机训练组训练12次后的步行速度。在目标2中，我们将量化影响 IC和跑步机训练在改善瘫痪肌肉激活和疲劳性方面的作用。由于增强了神经功能 肌肉的激活，我们预计瘫痪腿上的IC将提高力量和神经肌肉 疲劳性。最大膝关节伸肌扭矩产生(力量)和维持亚最大扭矩的能力 力量(疲劳性)将在目标1中描述的所有治疗组中进行评估。我们预计最大的收益 在力量和任务持续时间方面，中风IC跑步机组在12次训练后发生。最后，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健康。我们 假设IC跑步机训练将导致大鼠月国动脉血流介导的扩张增加 偏瘫小腿和非偏瘫手臂的臂动脉。随着肌肉活动的改善，我们 预测中风IC跑步机训练组将有增加的有氧能力，通过分级 运动试验测定最大摄氧量(VO2峰值)。这些研究将是第一个量化影响的研究 IC是一种非侵入性、易于管理、成本效益高的干预措施，对步行速度、运动功能和 慢性卒中患者的心肺功能。这项研究的发现有可能对 IC辅助步行功能后的神经康复策略 卒中。未来的研究将探讨IC的分子机制，以及IC在急性卒中中的作用 人群，以及IC与其他行走辅助装置的疗效比较。

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.