Collateral flow and stroke outcome

侧支血流和卒中结果

• 批准号: 9553470
• 负责人: JIALING LIU
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9553470
• 关键词: Acute; Adoptive Transfer; Affect; Anatomy; Antibodies; Biological; Blood Vessels; Bone Marrow Cells; Brain; C57BL/6 Mouse; CD36 gene; Centers for Disease Control and Prevention (U.S.); Cerebral Ischemia; Cerebrum; Chronic; Clinical; Collateral Circulation; Data; Defect; Development; Diabetes Mellitus; Diabetic mouse; Diagnosis; Disabled Persons; Disease; Exposure to; Financial compensation; Flow Cytometry; Foundations; Functional disorder; Future; Gene Expression; Genetic; Glucose; Hemorrhage; Herbicides; Hour; Hyperglycemia; Hypertension; Hypoglycemia; Impairment; Inbred BALB C Mice; Infarction; Inflammation; Inflammatory; Injury; Insulin; Investigation; Ischemic Brain Injury; Ischemic Stroke; Leukocytes; Link; Metabolic Diseases; Metabolic syndrome; Middle Cerebral Artery Infarction; Middle Cerebral Artery Occlusion; Military Personnel; Modeling; Mouse Strains; Mus; Non-Insulin-Dependent Diabetes Mellitus; Optical Coherence Tomography; Optics; Outcome; Oxidative Stress; Pathology; Patients; Pharmacology; Phenotype; Population; Regulation; Reporting; Risk; Risk Factors; Role; Services; Site; Stroke; Structure; System; TLR4 gene; Technology; Testing; Therapeutic Intervention; Thrombolytic Therapy; Up-Regulation; Veterans; agent orange; brain tissue; db/db mouse; diabetic; genetic variant; glycemic control; improved; inhibitor/antagonist; macrophage; middle cerebral artery; monocyte; public health relevance; recruit; response; stroke outcome; stroke risk; stroke trials; targeted treatment; therapeutic development; therapy development; tomography; treatment group

 DESCRIPTION (provided by applicant): Collateral status is an independent predictor of stroke outcome, as well as response to thrombolytic therapies in patients with ischemic stroke. Genetic factors contribute to the extent and development of native collaterals, whereas patients with metabolic syndromes are associated with poor collateral status during acute ischemic stroke. Diabetes increases the risk of stroke and exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Our preliminary data suggest that using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice and it continued to grow over the course of one week. However, an impairment of collateral recruitment was evident in the type-II-diabetic db/db mice immediately after MCAO. In the current application, we seek to investigate mechanisms underlying leptomeningeal collateral impairment. Aim1 will first determine the dynamics of retrograde flow compensation from ACA to MCA in the leptomeningeal collateral circulation after MCA stroke and their contribution to stroke outcome in mouse strains that can be used as surrogates for genetic variant of collateral circulation or for modeling pathophysiology in metabolic diseases. Aim 2 will decipher whether acute hyperglycemia contributes to the impairment of leptomeningeal collateral flow in the type II diabetic mice and whether short-term insulin therapy restores the collateral status after stroke. Aim 3 will determine the macrophage phenotype favorable for collaterogenesis/arteriogenesis via flow cytometry. We will also ascertain the role of CD36, a marker for M2 macrophage, in regulating collateral flow. Complementary approaches will determine whether by enhancing CD36 expression by pharmacological agent promote collateral flow in the diabetic mice or whether by adoptive transfer of control bone marrow cells into diabetic mice rescues the collateral status in the latter. This proof-of-concept study will provide a foundation for the development of therapeutic interventions to augment collateral flow for the treatment of ischemic stroke.

 描述（由申请人提供）： Genetti抵押品是一个独立的预测结果，并且对患者的rombolytic疗法的反应促进了天然侧支的延伸，而与代谢综合征的patiation”在急性缺血性糖尿病的风险中增加了。中风和加剧的缺血性脑损伤。 。在代谢性疾病中。药物NT的压缩促进了糖尿病小鼠的侧支流，或者是通过碰撞的collo胶在后者中的副作用，这将为治疗治疗的治疗治疗teschemic Streos的治疗提供基础。