Quantitation of Early Vascular Leakage after Stroke

中风后早期血管渗漏的定量

• 批准号: 6961558
• 负责人: Patrick D Lyden
• 金额: $ 20.04万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6961558
• 关键词: bioimaging /biomedical imaging; biomarker; blood brain barrier; blood flow measurement; brain circulation; brain imaging /visualization /scanning; cerebral ischemia /hypoxia; cerebrovascular occlusions; confocal scanning microscopy; dextrans; disease /disorder model; fibrin; fluoresceins; imidazole; immunocytochemistry; inflammation; intravital microscopy; laboratory rat; method development; microcirculation; neuropathology; pathologic process; selectins; somesthetic sensory cortex; stroke

DESCRIPTION (provided by applicant): Blood brain barrier breakdown is a common element in many neurological diseases; an extensive literature demonstrates temporal and/or spatial associations between the inflammatory processes that underly blood brain barrier breakdown and subsequent death of neural tissue (PAS-04-072). Further, recent longitudinal neuro-imaging studies in stroke patients indicate that early post-ischemic blood brain barrier breakdown correlates with an increased likelihood for hemorrhagic transformation and poor clinical outcome (Latour et al, Ann Neurol, 2004, in press). However, the temporal and spatial patterns of blood brain barrier break down are poorly characterized, and the underlying mechanisms that trigger these processes remain poorly understood. We propose to develop a new experimental method to quantify blood brain barrier breakdown after experimental stroke in the adult rat. The major goal of these studies is to develop quantitative methods to measure blood brain barrier breakdown and also preserve tissue morphology for correlative and quantitative immunocytochemical studies of tissue hypoxia, thrombosis and low blood flow. In this R21 developmental project, we will use a rat stroke model of reversible middle cerebral artery occlusion (MCAo) to develop measures of ischemic heterogeneity and test potential mechanisms underlying that heterogeneity. 1. Develop methods for the quantitation of local microvascular blood brain barrier break down. 2. Validate that areas of FITC-dextran blood brain barrier breakdown correlate with ischemic pathology by co-staining for markers of tissue hypoxia, vessel reactivity, and mircrothrombosis. 3. Validate that FITC-dextran blood brain barrier breakdown correlates with in vivo measures of low blood flow in microvessels.

描述（由申请人提供）：血脑屏障的崩溃是许多神经系统疾病的常见元素；广泛的文献表明，炎症过程之间的时间和/或空间关联，这些炎症过程是基本的血脑屏障分解和随后神经组织死亡的（PAS-04-072）。此外，最近对中风患者的纵向神经成像研究表明，早期缺血后血脑屏障的崩溃与出血转化和临床结果不佳的可能性增加相关（Latour等，Ann Neurol，2004年，印刷中）。然而，血脑屏障的分解的时间和空间模式的特征很差，触发这些过程的基本机制仍然很少理解。我们建议开发一种新的实验方法，以量化成年大鼠实验性中风后血液屏障的分解。这些研究的主要目的是开发定量方法来测量血脑屏障的分解，并保留组织形态的相关性和定量免疫细胞化学研究，以进行组织缺氧，血栓形成和低血流的相关性和定量免疫细胞化学研究。在这个R21发育项目中，我们将使用可逆性脑动脉闭塞（MCAO）的大鼠中风模型来开发该异质性的缺血性异质性和测试潜在机制的测量。 1。开发定量局部微血管血脑屏障的方法。 2。验证FITC-DEXTRAN血脑屏障的区域通过共同染色的组织缺氧，血管反应性和mircrothrombombosis的标记与缺血性病理相关。 3。验证该FITC-二克血液脑屏障的分解与微血管中低血流量的体内度量相关。