Evaluation of Antioxidant Suppl in Focal CNS Ischemia

局灶性中枢神经系统缺血抗氧化剂供应的评价

• 批准号: 6661339
• 负责人: WAYNE M CLARK
• 金额: $ 18.88万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6661339
• 关键词: alternative medicine; anticoagulants; antioxidants; aspirin; brain circulation; cardiovascular disorder risk; central nervous system; cerebral hemorrhage; cerebral ischemia /hypoxia; combination therapy; dietary supplements; disease /disorder model; dosage; enzyme linked immunosorbent assay; fatty acids; flow cytometry; ginkgo biloba; inflammation; laboratory mouse; messenger RNA; neuroprotectants; nonhuman therapy evaluation; nutrition related tag; outcomes research; placebos; polymerase chain reaction; stroke therapy; ultrasound blood flow measurement

DESCRIPTION (provided by applicant): Stroke is a major cause of death and disability in the United States. Evidence suggests that even if blood flow is initially restored additional "reperfusion injury" processes can occur that can potentiate brain injury and reduce existing blood flow. Some of the mediators of this "reperfusion injury" appear to be due to an inflammatory responsive involving free radical generation, activated leukocytes, and platelet activated factor. Various commercially available "antioxidant supplements" appear to produce clinical benefit in several diseases. These supplements including Ginkgo biloba extract (EGb) and alpha lipoic acid (LA) have multitude of biologic effects including reducing free radical generation, inhibiting PAF and leukocyte activation (inhibit NFalphaB), and improving cerebral blood flow. Antioxidants have shown benefits in multiple disease models involving reperfusion injury but have yet to be fully evaluated in reperfusion injury related to stroke. This project will investigate the treatment potential and protective mechanisms of selected antioxidants using an animal model that closely approximates clinical stroke. The specific aims of the study are as follows: Aim 1: To confirm and characterize the neuroprotective efficacy of EGb in focal CNS ischemia, determine the effects of EGb on the inflammatory response and CBF, and evaluate safety interventions with other medications used in stroke. Aim 2: To confirm and characterize the neuroprotective efficacy of LA and dihydro lipoic (DHLA) in focal CNS ischemia and determine their effects on the inflammatory response and CBF. This study will use the middle cerebral artery filament occlusion (MCAO) model in the mouse and will utilize a combination of ischemic damage (lesion size) and neurologic functional measurements to determine efficacy. Potential mechanisms of efficacy for each antioxidant will be assessed including effects on in vivo cerebral blood flow (laser doppler measurement of blood flow) and the inflammatory response (molecular and flow cytometry). The information obtained from this project will be critical in planning future clinical stroke trials involving these agents.

描述（由申请人提供）：中风是导致死亡的主要原因