Quantitation of Early Vascular Leakage after Stroke

中风后早期血管渗漏的定量

• 批准号: 7140319
• 负责人: Patrick D Lyden
• 金额: $ 16.3万
• 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 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140319
• 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）：血脑屏障破坏是许多神经系统疾病的常见因素；大量文献表明，血脑屏障破坏的炎症过程与随后的神经组织死亡之间存在时间和/或空间关联（PAS-04-072）。此外，最近对中风患者进行的纵向神经影像学研究表明，缺血后早期血脑屏障破坏与出血性转化可能性增加和不良临床结果相关（Latour 等人，Ann Neurol，2004 年，出版中）。然而，血脑屏障破坏的时间和空间模式尚不清楚，而且触发这些过程的潜在机制仍知之甚少。我们建议开发一种新的实验方法来量化成年大鼠实验性中风后血脑屏障的破坏。这些研究的主要目标是开发定量方法来测量血脑屏障的破坏，并保留组织形态，用于组织缺氧、血栓形成和低血流量的相关和定量免疫细胞化学研究。在这个 R21 开发项目中，我们将使用可逆性大脑中动脉闭塞 (MCAo) 的大鼠中风模型来开发缺血异质性的测量方法并测试该异质性背后的潜在机制。 1. 开发局部微血管血脑屏障破坏的定量方法。 2. 通过对组织缺氧、血管反应性和微血栓形成标记物进行共染色，验证 FITC-葡聚糖血脑屏障破坏区域与缺血性病理学相关。 3. 验证 FITC-葡聚糖血脑屏障破坏与微血管低血流的体内测量结果相关。