Hemorheological Factors in Cerebral Ischemia

脑缺血的血液流变学因素

基本信息

批准号：
10401287
负责人：
David Hastings Cribbs
金额：
$ 60.9万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10401287
关键词：
Actins Address Age Aging Alzheimer&apos s Disease Animal Model Animals Area Arterial Disorder Biomedical Engineering Biometry Blood Vessels Brain Brain Diseases Brain hemorrhage CD47 gene Cell Culture Techniques Cerebral Amyloid Angiopathy Cerebral Ischemia Cerebrum Chronic Kidney Failure Clinical Cytoskeleton Deposition Development Disease Endothelial Cells Endothelium Erythrocytes Event Executive Dysfunction Functional disorder Funding Future Gelatinase B Goals Grant Hemorrhage Hemosiderin Human Hypertension Imaging Techniques Impaired cognition Impairment In Vitro Individual Intercellular Junctions Investigation Iron Knowledge Lead Link Literature Magnetic Resonance Imaging Mediating Microglia Microvascular Dysfunction Modeling Morbidity - disease rate Nephrology Neurobiology Neurologic Pathogenesis Pathologic Patient Care Patients Phosphatidylserines Physiology Prevention Process Proteins PubMed Recording of previous events Research Personnel Risk Risk Factors Role Series Source Stroke Subcortical Infarctions Subcortical Leukoencephalopathy Techniques Testing Urea White Matter Disease Work age related aged brain dysfunction cerebral microbleeds cerebrovascular clinically significant design expectation experimental study in vitro Model in vivo innovation insight interest monolayer multidisciplinary neuropathology novel stroke neurology stroke risk success synergism targeted treatment theories treatment program vascular risk factor

项目摘要

Project Summary/Abstract This project (begun in 1984) continues its long-term goal to enhance understanding of stroke by novel mechanistic investigations. Our principal interest is cerebral microhemorrhage, the pathological substrate of cerebral microbleeds and the major hemorrhagic component of microvascular cerebral disease. The proposed project will utilize a combination of novel animal models of cerebral microbleeds, new cell culture models of microbleeds that address red blood cell (RBC)-endothelial interactions, and cutting edge analytic techniques. Our objective is to identify mechanisms that broadly impact development of cerebral microbleeds as well as those more specifically related to individual vascular risk factors for microbleeds, The project investigators are a unique group of investigators with expertise in stroke neurology, vascular neurobiology, nephrology, bioengineering, and biostatistics, all with capabilities relevant to animal and cell culture studies. We specifically propose the following aims: Specific Aim 1: To determine mechanisms of cerebral microhemorrhage in vivo. Specific Aim 2: To delineate paracellular mechanisms of RBC passage across brain microvascular endothelium in vitro. Specific Aim 3: To delineate transcellular mechanisms of RBC passage across brain microvascular endothelium. The proposed studies are designed as a series of synergistic experiments that combine in vivo and in vitro studies to provide novel insights into microvascular brain disease. We will use a combination of studies of microvascular physiology and neuropathology to identify the vascular source of cerebral microbleeds and to delineate those interactions between RBC and brain microvascular endothelium that immediately precede establishment of cerebral microbleeds. The project is a direct extension of work we completed during the most recent funding period of this grant and incorporate new animal models of cerebral microbleeds and novel conceptual models describing microbleed pathogenesis. Our in vivo studies will address mechanisms of aging, hypertension, and chronic kidney disease in microbleed development, along with the roles of microglia and matrix metalloproteinase-9. This project directly addresses the highly prevalent problem of hemorrhagic microvascular disease of the brain. Our work and that of others have shown the near-ubiquitous presence of microhemorrhagic changes in aging human brain. Our multi-disciplinary team of investigators are uniquely capable of taking this project to completion, directly testing our microbleed conceptual models in the expectation that robust insights will emerge helping to transform the management of microvascular disorders of the brain which, along with Alzheimer’s disease, represents the most common cause of neurological morbidity of aging.

项目摘要/摘要该项目（始于1984年）继续其长期目标，以增强新颖的理解机械投资。我们的主要兴趣是脑微毛发，是脑微血管和微血管脑疾病的主要出血成分。提议项目将利用新型脑微粒动物模型的组合，新的细胞培养模型处理红细胞（RBC） - 内皮相互作用和尖端分析技术的微粒。我们的目的是确定广泛影响脑微粒发展的机制以及那些与微型细胞的单个血管危险因素更具体相关的项目，项目调查人员是具有中风神经学专业知识，血管神经生物学，肾脏科学专业知识的独特研究者生物工程和生物统计学，都具有与动物和细胞培养研究有关的能力。我们特别提出以下目的：特定目的1：确定体内脑微毛的机制。特定目的2：描述RBC通道横穿脑微血管的细胞细胞机制体外内皮。特定目的3：描绘RBC通道跨大脑微血管的跨细胞机制内皮。拟议的研究被设计为一系列协同实验，这些实验结合了体内和体外研究可提供对微血管脑疾病的新见解。我们将结合微血管生理学和神经病理学，以鉴定脑微孔的血管来源描绘RBC和脑微血管内皮之间的相互作用，紧接建立脑微孔。该项目是我们最多完成的工作的直接扩展该赠款的最新资金期并纳入了脑微孔和新颖的新动物模型描述微孔发病机理的概念模型。我们的体内研究将解决微胶质细胞的衰老，高血压和慢性肾脏疾病以及小胶质细胞的作用和基质金属蛋白酶9。该项目直接解决了高度普遍的出血微血管疾病的问题大脑。我们的作品和其他工作表现出了微观的近乎语言的存在衰老人脑的变化。我们的多学科研究人员团队具有独特的能力在期望强大的见解的期望下，要完成，直接测试我们的微孔概念模型的项目将出现有助于改变大脑微血管疾病的管理阿尔茨海默氏病是衰老神经系统发病率的最常见原因。