Vascular Contributions to Enriched Rehabilitation in Hypertension

血管对高血压康复的贡献

• 批准号: 10230439
• 负责人: Victoria L Wolf
• 金额: $ 6.64万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10230439
• 关键词: Address; Affect; Animals; Attenuated; Blood Vessels; Brain; Brain-Derived Neurotrophic Factor; Cerebrovascular Disorders; Clinical; Cognitive; Coupling; Data; Degenerative Disorder; Dementia; Development; Disease; Endothelial Cells; Endothelium; Event; Exposure to; Faculty; Fellowship; Female; Gait; Goals; Housing; Hypertension; Immunohistochemistry; Impaired cognition; Inbred SHR Rats; Intervention; Ischemic Brain Injury; Ischemic Stroke; Knowledge; Laboratories; Learning; Measures; Mediating; Mediator of activation protein; Medical; Medicine; Memory; Methods; Middle Cerebral Artery Occlusion; Modality; Modeling; Molecular; Motor; Movement; Neurologic; Outcome; Pathology; Patients; Pharmacology; Physical Rehabilitation; Positioning Attribute; Pre-Clinical Model; Procedures; Recovery; Recovery of Function; Rehabilitation therapy; Research; Risk Factors; Role; Signal Transduction; South Carolina; Stroke; System; Technical Expertise; Testing; Therapeutic; Training; Translational Research; Universities; Vascular Cognitive Impairment; Vascular Diseases; Vascularization; Work; base; behavior test; brain health; brain repair; cardiovascular risk factor; career; cerebrovascular; cognitive function; comorbidity; design; environmental enrichment for laboratory animals; experimental study; follow-up; functional outcomes; improved; innovation; kinematics; knock-down; long term memory; male; motor rehabilitation; neurotrophic factor; neurovascular; novel; object recognition; physically handicapped; post stroke; post stroke cognitive impairment; pre-clinical; pre-clinical research; prevent; programs; receptor; rehabilitation paradigm; rehabilitation strategy; response; restoration; sex; small hairpin RNA; stroke recovery; vascular contributions

Project Summary/Abstract This project is designed to address a gap in vascular contributions to cognitive impairment/dementia (VCID) research by determining the role and vascular mechanisms by which rehabilitation impacts post-stroke cognitive impairment, a principal VCID, in hypertension, the leading comorbid disease in patients with VCID and stroke. The central hypothesis is that enriched rehabilitation prevents profound progressive post-stroke cognitive impairment and improves functional outcomes in hypertensive animals via restoration of mature brain-derived neurotrophic factor (BDNF)-dependent vasotrophic coupling. In order to test this hypothesis, the proposal contains two specific aims to determine (1) the impact of ER on functional recovery after ischemic brain injury in hypertension and (2) the role of the BDNF system in the vascular contributions of ER-mediated recovery after ischemic brain injury in hypertension. Male and female spontaneously hypertensive rats (SHRs) will undergo either middle cerebral artery occlusion (MCAO) or sham procedure and be exposed to either standard housing conditions or a rehabilitation intervention with a combination of environmental enrichment and reach training for 5 weeks and 4 weeks of follow up. Cognitive and sensorimotor functional outcomes will be assessed by behavioral tests (novel object recognition, y-maze, Catwalk, and single-pellet reach task) for short- and long- term memory/learning in addition to kinematic analysis of paw movements and gait. A variety of molecular methods, including immunohistochemistry, will be used to identify potential mediators of the angiogenic and neurotrophic components of the recovery response to ER following MCAO. BDNF is one promising mechanistic target in VCID research. An endothelial cell-specific shRNA silencing approach will be used to examine the role of BDNF in the recovery response to ER. The applicant will complete the experiments outlined in this proposal under the guidance of her sponsor, Dr. Adviye Ergul, in the Department of Pathology & Laboratory Medicine at the Medical University of South Carolina. The applicant plans to utilize the technical skills and professional development she gains during the fellowship training to transition to a junior faculty position with a focus on translational VCID research. The long-term career goal of the applicant is to ultimately develop and maintain an independent research program that will contribute to our fundamental knowledge of the critical role of the vasculature in rehabilitation interventions in order to reduce the burden of cardio/cerebrovascular diseases.

项目摘要/摘要 该项目旨在解决认知障碍/痴呆症（VCID）的血管贡献差距 通过确定康复影响后认知的作用和血管机制来进行研究 损害是高血压的主要VCID，是VCID和中风患者的主要合并症。 中心假设是，富集的康复阻碍了势头的深刻渐进后认知 通过恢复成熟的大脑衍生的损害并改善高血压动物的功能结果 神经营养因子（BDNF）依赖性血性偶联。为了检验这一假设，该提议 包含两个具体目的，以确定（1）ER对缺血性脑损伤后功能恢复的影响 高血压和（2）BDNF系统在ER介导的恢复的血管贡献中的作用 高血压中缺血性脑损伤。雄性和女性自发性高血压大鼠（SHR）将发生 大脑中动脉闭塞（MCAO）或假手术，并接触到任何标准外壳 条件或康复干预措施与环境丰富和到达培训的结合 5周零4周的随访。认知和感觉运动功能结果将由 短期和长期的行为测试（新颖的对象识别，Y迷宫，时装秀和单重触及任务） 术语记忆/学习除了对PAW运动和步态的运动学分析。各种分子 包括免疫组织化学在内的方法将用于识别血管生成的潜在介体和 MCAO后ER的恢复反应的神经营养成分。 BDNF是一种有前途的机械 VCID研究的目标。内皮细胞特异性shRNA沉默方法将用于检查角色 BDNF在对ER的恢复响应中的。申请人将完成本提案中概述的实验 在她的赞助商的指导下，Adviye Ergul博士在病理与实验室医学系 南卡罗来纳州医科大学。申请人计划利用技术技能和专业人士 她在奖学金培训期间获得的发展，以过渡到初级教师职位，重点是 翻译VCID研究。申请人的长期职业目标是最终发展和维护 独立的研究计划将有助于我们对有关的基本知识 康复干预中的脉管系统，以减轻心脏/脑血管疾病的负担。