EFFECTS/EXERCISE/ENDOTHELIAL FUNCTION IN STROKE PATIENTS

描述(申请人提供)：候选人：弗雷德里克·M·艾维，博士，马里兰大学巴尔的摩分校老年学系助理教授。应聘者的长期职业目标是在专注于中风、运动、胰岛素-葡萄糖代谢和心血管危险因素修改的研究环境中取得学术进步。艾维博士最近加入了该部门的教员队伍，这使得现在是他职业生涯中这个RCA提供临床和实验室调查方面的高级研究培训的理想时机。候选人的当务之急是在有经验的导师的指导下，研究运动对慢性偏瘫中风患者动脉粥样硬化血栓形成风险的影响机制。背景：在美国，中风是导致残疾和死亡的首要原因。中风后缺乏运动会增加高胰岛素血症和胰岛素抵抗综合征的发生率，这会损害内源性纤维蛋白溶解和血管舒缩功能，从而增加中风和心肌梗死复发的风险。目前预防中风复发和M1的策略是有限的。尽管有氧运动(AEX)改善了健康老年人的纤溶、一氧化氮相关血管运动反应性(NO-VMR)和胰岛素敏感性，但先前还没有研究表明有氧运动对慢性偏瘫中风患者血管内皮细胞功能和胰岛素-葡萄糖代谢的影响。我们的初步数据首次证明，在接受AEX训练的慢性偏瘫中风患者中，内源性纤溶功能得到改善，高胰岛素血症有所降低。假设：在建议的RCA中，候选人调查了这样的假设，即6个月跑步机AEX改善了慢性偏瘫中风患者的内源性纤溶和一氧化氮相关的VMR，并且这些变化与全身和组织水平上胰岛素介导的葡萄糖代谢的改善有关。其具体目的是：1)确定6个月的AEX对a)纤溶曲线和b)脑循环中NO-VMR的影响。2)确定AEX对全身胰岛素作用的影响，以及纤溶和NO-VMR的改变是否与运动引起的胰岛素水平和作用有关。3)确定偏瘫和AEX对卒中骨骼肌胰岛素信号蛋白的影响。环境：老年病学部拥有在老龄化、中风、运动、新陈代谢和血管研究方面进行高级研究培训的极佳资源。分子医学方面的额外培训由Shuldiner博士和McLenithan博士推动，他们是修订提案的共同导师。

DESCRIPTION (provided by applicant): Candidate: Frederick M. Ivey, Ph.D. is an Assistant Professor in the Division of Gerontology, School of Medicine at the University of Maryland, Baltimore. The long-term career goal of the candidate is to advance academically in a research environment focusing on stroke, exercise, insulin-glucose metabolism, and cardiovascular risk factor modification. Dr. Ivey has recently joined the faculty in the Division, making this the ideal time in his career for this RCA to provide advanced research training in clinical and laboratory investigation. The candidate's immediate goat is to examine the mechanisms by which exercise afibcts atherothrombotic risk in chronic hemiparetic stroke patients under the guidance of experienced mentors. Background: Stroke is the leading cause of disability and thkd leading cause of death in the United States. Physical inactivity following stroke increases the incidence of hyperinsulinemia and the insulin resistance syndrome, which increases risk for recurrent stroke and MI by impairing endogenous fibrinoiysis and vasomotor function. Current strategies for preventing recurrent stroke and M1 are limited. Although aerobic exercise (AEX) improves fibrinolysis, nitric oxide-related vasomotor reactivity (NO-VMR), and insulin sensitivity in the healthy elderly, no prior studies have addressed the effects of AEX therapy on vascular endothelial celt function and insulin-glucose metabolism in chronic hemiparetic stroke patients. Our preliminary data provides the first evidence of improved endogenous fibrinolysis and reduced hyperinsulinemia in chronic hemiparetic stroke patients with AEX training. Hypothesis: In the proposed RCA the candidate investigates the hypothesis that 6 months treadmill AEX improves endogenous fibrinolysis and nitric oxide-related VMR in chronic hemiparetic stroke patients, and that these changes are related to improved insulin mediated glucose metabolism on both the whole body and tissue levels. The specific aims are to: 1) Determine the effects of 6 months AEX on a) fibrinolysis profiles and b) NO-VMR in the cerebral circulation. 2) Determine the effects of AEX on whole body insulin action, and whether alterations in fibrinolysis and NO-VMR are related to exercise-induced changes in insulin levels and action 3) Determine the effects of hemiparesis and AEX on insulin signaling proteins in stroke skeletal muscle. Environment: The Division of Gerontology has excellent resources for advanced research training in aging, stroke, exercise, metabolic, and vascular research. Additional training in molecular medicine is facilitated by Drs. Shuldiner and McLenithan, co-mentors on the revised proposal.