Aerobic Training to Improve Energy Utilization and Antioxidant Capacity in Stroke

描述 15%到30%的中风幸存者是永久性残疾的，这通常导致中风后久坐不动的生活方式和功能依赖。虽然已知偏瘫步态使步行活动的能量消耗增加1.5-2倍，但慢性中风如何影响总的日常能量消耗(TDEE)和饮食摄入量目前尚不清楚。能量平衡的改变(消耗摄入)可能会导致底物氧化和骨骼肌氧化应激的损害。骨骼肌氧化应激增加与疲劳、心血管和肌肉耐力下降有关。在老年、非中风人群中，跑步机运动训练改善了家庭步行活动、身体功能和代谢特征，并对骨骼肌具有抗氧化作用。此外，确保能量和常量营养素的摄入量满足个人的能量和燃料需求可能会减少氧化损伤。这项随机对照研究测试了这样的假设，即跑步机康复加营养修改(“心脏健康”饮食加充足蛋白质)(TM+N)与拉伸加营养修改(ST+N)(营养对照)将1)改善能量平衡和底物氧化，2)减少全身和组织水平的氧化应激，3)这些干预措施(TM+N和ST+N)与跑步机(TM)和拉伸(ST)对照的分别比较，从她导师目前的R01将支持营养修改在中风中的康复作用。我们提出以下目标：目标1：评估TM+N与ST+N治疗6个月对慢性卒中幸存者TDEE和底物氧化的影响。目的：比较TM+N与ST+N治疗6个月对慢性卒中存活者全身和组织氧化应激及抗氧化能力的影响。目的：比较TM+N和ST+N与单独应用TM和ST对慢性卒中存活者能量平衡及全身和组织氧化应激的影响。将招募年龄较大(55-75岁)、患有慢性中风(中风后至少6个月)的男性和绝经后女性(n=50)，并有稳定的神经功能障碍。受试者将随机参加6个月的饮食调整(30%的卡路里为脂肪，10%的卡路里为饱和脂肪，&lt；2400毫克钠，25g/d纤维，1.0-1.2g/kg/d的瘦肉蛋白质)+有氧运动训练或饮食修改+全身伸展。七天的加速测量和饮食记录将被用来确定能量平衡。间接量热法将被用来确定禁食和高峰期和次高峰期运动量的底物氧化。将进行抽血和偏瘫和非偏瘫股外侧肌骨骼肌活组织检查，以确定运动康复或拉伸后全身和组织水平氧化应激含量(硝酸盐/亚硝酸盐和硫代巴比妥酸反应物质)和抗氧化能力(超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶)的变化。 在慢性中风幸存者中。CDA-2申请中描述的指导和培训将极大地促进被提名者发展为独立的研究人员，同时确定有氧运动康复和营养修改可以改善TDEE和减少氧化应激的机制。我们推测，这项研究将为改善中风治疗、底物利用以及血液和骨骼肌的抗氧化能力提供证据，并减少中风老兵的身体活动不足，潜在地降低与护理慢性中风致残退伍军人相关的临床成本。

DESCRIPTION Fifteen to 30% of stroke survivors are permanently disabled, which usually leads to a sedentary lifestyle and functional dependence following stroke. While it is known that hemiparetic gait elevates the energy cost of ambulatory activity by 1.5- 2 fold, how chronic stroke affects total daily energy expenditure (TDEE) and dietary intake is currently unknown. Altered energy balance (expenditure ` intake) may result in impaired substrate oxidation and skeletal muscle oxidative stress. Elevated oxidative stress in skeletal muscle is associated with fatigue and decreased cardiovascular and muscular endurance. Treadmill exercise training in older, non-stroke populations improves home ambulatory activity, physical function, and metabolic profiles and has antioxidant effects in skeletal muscle. Additionally, ensuring that energy and macronutrient intake meets an individual's energy and fuel needs may result in decreases in oxidative damage. This randomized control study tests the hypothesis that treadmill rehabilitation plus nutritional modification ("heart healthy" diet plus adequate protein) (TM+N) versus stretching plus nutritional modification (ST+N) (nutrition control) will 1) improve energy balance and substrate oxidation, 2) reduce systemic and tissue level oxidative stress, and 3) that the respective comparison of these interventions (TM+N and ST+N) to treadmill (TM) and stretching (ST) controls from her mentor's current R01 will support the rehabilitative role of nutritional modification in stroke. We propose the following aims: Aim 1: To assess the effects of six months of TM+N versus ST+N on TDEE and substrate oxidation in chronic stroke survivors. Aim 2: To examine the effects of six months of TM+N versus ST+N on systemic and tissue oxidative stress and antioxidant capacity in chronic stroke survivors. Aim 3: To compare the effects of TM+N and ST+N versus TM and ST alone, respectively, on energy balance and systemic and tissue oxidative stress, in chronic stroke survivors. Older (55-75 years), men and postmenopausal women (n=50) with chronic stroke (at least 6 months post stroke) with stable neurological deficits will be recruited. Subjects will be randomized to participate in six months o dietary modification (<30% of calories as fat, <10% as saturated fat, <2,400 mg sodium, 25 g/d of fiber, and 1.0-1.2 g/kg/d of lean protein) plus aerobic exercise training or dietary modificatio plus whole body stretching. Seven-day accelerometry and dietary records will be used to determine energy balance. Indirect calorimetry will be used to determine substrate oxidation during fasting and a peak and submaximal exercise bout. Blood draws and paretic and non-paretic vastus lateralis skeletal muscle biopsies will be performed to determine changes in systemic and tissue level oxidative stress content (nitrate/nitrite and thiobarbituric acid reactiv substances) and antioxidant capacity (superoxide dismutase, glutathione peroxidase, and catalase) following exercise rehabilitation or stretching with and without nutritional modification in chronic stroke survivors. The mentoring and training described in this CDA-2 application will greatly enhance the nominee's development into an independent investigator, while simultaneously identifying mechanisms by which aerobic exercise rehabilitation with nutritional modification can improve TDEE and reduce oxidative stress. We postulate that this study will provide evidence to improve stroke treatment, substrate utilization, and the antioxidant capacity of blood and skeletal muscle and reduce physical inactivity in Veteran stroke survivors, potentially leading to a reduction in clinical costs related to the care of Veterans with disabilit from chronic stroke.