EFFECTS/EXERCISE/ENDOTHELIAL FUNCTION IN STROKE PATIENTS

描述（由申请人提供）：候选人：弗雷德里克M。Ivey博士是位于巴尔的摩的马里兰州大学医学院老年学系的助理教授。候选人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饰的研究环境中取得学术进步。Ivey博士最近加入了该部门的教师队伍，这是他职业生涯中的理想时机，为RCA提供临床和实验室调查方面的高级研究培训。候选人的直接目标是在有经验的导师的指导下，研究运动抑制慢性偏瘫中风患者动脉粥样硬化血栓形成风险的机制。背景：在美国，中风是导致残疾和死亡的主要原因。中风后缺乏体力活动会增加高胰岛素血症和胰岛素抵抗综合征的发生率，这会通过损害内源性胰岛素溶解和血管功能而增加复发性中风和MI的风险。目前预防复发性卒中和M1的策略有限。尽管有氧运动（AEX）可以改善健康老年人的纤溶、一氧化氮相关血管反应性（NO-VMR）和胰岛素敏感性，但目前尚无研究探讨AEX治疗对慢性脑卒中偏瘫患者血管内皮细胞功能和胰岛素-葡萄糖代谢的影响。我们的初步数据提供了第一个证据，改善内源性纤维蛋白溶解和减少高胰岛素血症的慢性偏瘫中风患者与AEX训练。假设：在拟议的RCA中，候选人研究了以下假设：6个月跑步机AEX改善慢性轻偏瘫卒中患者的内源性纤维蛋白溶解和一氧化氮相关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改善相关。具体目的是：1）确定6个月AEX对a）脑循环中纤维蛋白溶解特征和B）NO-VMR的影响。2)确定AEX对全身胰岛素作用的影响，以及纤维蛋白溶解和NO-VMR的改变是否与运动诱导的胰岛素水平和作用的变化有关3）确定轻偏瘫和AEX对中风骨骼肌中胰岛素信号蛋白的影响。工作环境：老年医学部拥有优秀的资源，可用于衰老、中风、运动、代谢和血管研究方面的高级研究培训。Shuldiner博士和McLenithan博士是修订提案的共同导师，他们为分子医学提供了额外的培训。

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.