Biomarkers of Vasospasm and Outcome following Subarachnoid Hemorrhage

血管痉挛的生物标志物和蛛网膜下腔出血后的结果

• 批准号: 8093214
• 负责人: Sherry Hsiang-Yi Chou
• 金额: $ 17.88万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8093214
• 关键词: Actins; Affect; Age; American; Angiography; Back; Big Endothelin; Biological Markers; Blood; Blood Circulation; Brain Injuries; Cerebrospinal Fluid; Cerebrovascular Spasm; Cleaved cell; Clinical; Critical Care; Critical Illness; Data; Diagnosis; Diagnostic; Diagnostic tests; Endothelin-1; Foundations; Future; Gelatinase A; Gelatinase B; Gelsolin; Goals; Human; In Vitro; Incidence; Inflammation; Inflammatory; Inflammatory Response; Injury; Interleukin-6; Lead; Leukocytes; Life; Matrix Metalloproteinases; Measures; Mediating; Molecular; Morbidity - disease rate; Neurologic; Outcome; Pathogenesis; Pathway interactions; Patients; Physicians; Plasma; Play; Reaction; Recruitment Activity; Risk; Role; Sampling; Secondary to; Societies; Stroke; Subarachnoid Hemorrhage; Survivors; Techniques; Testing; Therapeutic; Time; Tumor Necrosis Factor-alpha; Vasospasm; White Blood Cell Count procedure; Work; cohort; cytokine; disability; extracellular; feeding; functional outcomes; high risk; improved; mathematical model; mortality; new technology; novel; predictive modeling; prospective; response; years of life lost

DESCRIPTION (provided by applicant): Subarachnoid hemorrhage (SAH) affects over 30,000 Americans per year and is one of the major causes of stroke-related potential life-years lost in people age 65 and younger. Despite advances in critical care for SAH patients, more than half of SAH survivors still live with significant disability. Vasospasm, which can occur in up to 70% of SAH survivors, is one of the most important causes for additional brain injury and disability after SAH. Currently, there are no diagnostic tests that can identify SAH patients at risk for developing vasospasm. The diagnosis and treatment of vasospasm are high-risk and often invasive. The causes of vasospasm and secondary brain injury and disability following SAH remain incompletely understood. In this study, we examine specific molecular biomarkers from blood and cerebrospinal fluid samples collected from SAH subjects in order to understand their potential role in causing vasospasm and secondary brain injury following SAH. We will recruit 200 patients with SAH, bank their available blood and cerebrospinal fluid samples, and use advanced molecular techniques to analyze and detect potentially novel molecular biomarkers. Our first aim is to examine the relationship between vasospasm seen on angiogram with white blood cells' release of matrix metalloproteinases (MMPs) which can cleave endothelin-1 into fragments that can subsequently cause spasm of cerebral arteries. Our second aim is to correlate SAH-related disability with white blood cells' release of MMPs and their interactions with cytokines, plasma gelsolin, and actin - molecules that mediate inflammatory reaction in critical illness such as SAH. Finally, we will use the data generated through our first 2 aims to build a mathematical model aimed to help physicians identify SAH patients who are at high risk for developing vasospasm and further disability. We hope results of this study will advance our understanding on important molecular mechanisms that lead to vasospasm and to secondary brain injuries in SAH. Our work will lay the foundation for potential discovery of new non-invasive bedside tests that can better diagnose and predict vasospasm and patients at risk for greater disability following SAH. Ultimately, we hope advances in understanding of molecular mechanisms of vasospasm and secondary brain injury following SAH will help us identify new therapies that may improve survival and reduce disability in SAH patients. PUBLIC HEALTH RELEVANCE: Subarachnoid hemorrhage (SAH) affects over 30,000 Americans per year and leaves many victims in significant long term disability. This study uses novel technology to search for causes and potential cure of brain injury and disability caused by SAH.

描述（由申请人提供）：蛛网膜下腔出血（SAH）每年影响超过30，000名美国人，是65岁及以下人群中与卒中相关的潜在生命年损失的主要原因之一。尽管SAH患者的重症监护取得了进展，但超过一半的SAH幸存者仍然患有严重残疾。血管痉挛可发生在高达70%的SAH幸存者中，是SAH后额外脑损伤和残疾的最重要原因之一。目前，没有诊断测试可以识别SAH患者发生血管痉挛的风险。血管痉挛的诊断和治疗是高风险的，并且通常是侵入性的。蛛网膜下腔出血后血管痉挛、继发性脑损伤和残疾的原因仍不完全清楚。 在这项研究中，我们研究了从SAH受试者收集的血液和脑脊液样本中的特定分子生物标志物，以了解它们在SAH后引起血管痉挛和继发性脑损伤中的潜在作用。我们将招募200名SAH患者，储存他们可用的血液和脑脊液样本，并使用先进的分子技术分析和检测潜在的新型分子生物标志物。我们的第一个目的是研究血管造影所见的血管痉挛与白色血细胞释放基质金属蛋白酶（MMPs）之间的关系，MMPs可以将内皮素1切割成片段，随后引起脑动脉痉挛。我们的第二个目的是将SAH相关的残疾与白色血细胞释放MMP及其与细胞因子、血浆凝溶胶蛋白和肌动蛋白的相互作用相关联，所述细胞因子、血浆凝溶胶蛋白和肌动蛋白分子介导诸如SAH的危重疾病中的炎症反应。最后，我们将使用通过我们的前2个目标生成的数据来建立一个数学模型，旨在帮助医生识别具有发生血管痉挛和进一步残疾的高风险的SAH患者。 我们希望这项研究的结果将促进我们对导致SAH中血管痉挛和继发性脑损伤的重要分子机制的理解。我们的工作将为潜在发现新的非侵入性床边测试奠定基础，这些测试可以更好地诊断和预测血管痉挛以及SAH后有更大残疾风险的患者。最终，我们希望在SAH后血管痉挛和继发性脑损伤的分子机制方面的进展将有助于我们确定可能改善SAH患者生存率和减少残疾的新疗法。 公共卫生关系：蛛网膜下腔出血（SAH）每年影响超过30，000名美国人，并使许多受害者长期残疾。本研究使用新技术寻找SAH引起脑损伤和残疾的原因和潜在治疗方法。