The role of neutrophils in SAH

中性粒细胞在 SAH 中的作用

• 批准号: 7535499
• 负责人: Jose Javier Provencio
• 金额: $ 16.97万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-02 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7535499
• 关键词: Accounting; Address; Admission activity; Aneurysmal Subarachnoid Hemorrhages; Astrocytes; Biological Assay; Blood; Blood Circulation; Blood Vessels; Blood donor; Blood specimen; Brain; CXCL1 gene; Cerebral Aneurysm; Cerebral Ischemia; Cerebrospinal Fluid; Cerebrovascular Spasm; Cerebrum; Clinical; Collection; Complex; Complication; Development; Disease; Doctor of Medicine; Dose; Drug Delivery Systems; Enzyme-Linked Immunosorbent Assay; Enzymes; Event; Experimental Models; Flow Cytometry; Functional disorder; Generations; Goals; Head; Hemorrhage; Human; Hydroxyl Radical; IL8 gene; IL8RB gene; Imaging Techniques; Inflammation; Inflammatory; Inflammatory Response; Injury; Investigation; Knockout Mice; Knowledge; Lead; Lipids; Liquid substance; Mass Spectrum Analysis; Mediating; Modeling; Monitor; Morbidity - disease rate; Mus; NADPH Oxidase; Neurologic; Neutrophil Activation; Neutrophil Infiltration; Nitrates; Nitric Oxide; Nitrites; Nucleic Acids; Oxidants; Pathogenesis; Pathway interactions; Patients; Pattern; Peroxidases; Phenylalanine; Physicians; Physiology; Post-Translational Protein Processing; Production; Proteins; Recruitment Activity; Relative (related person); Reporting; Research Personnel; Research Training; Risk; Role; Rupture; Sampling; Scientist; Severities; Source; Stroke; Subarachnoid Hemorrhage; Subarachnoid Space; Superoxides; Syndrome; Testing; Therapeutic; Time; Tissues; Tyrosine; United States; Vascular Endothelial Cell; Vasospasm; Wild Type Mouse; base; career; chemokine; chemokine receptor; cohort; disability; effective therapy; inflammatory marker; information gathering; insight; molecular marker; mortality; mouse model; neutrophil; prevent; programs; research study; tool; vasoconstriction

Subarachnoid hemorrhage is the third leading cause of stroke in the United States but accounts for fifty percent of the mortality and morbidity in cerebral vascular events. The syndrome of delayed cerebral ischemia (vasospasm) is a common, dangerous and poorly understood complication of subarachnoid hemorrhage. Neutrophil infiltration is the predominant early inflammatory response in subarachnoid hemorrhage; however, the role of neutrophils and their products in mediating vasospasm has not been elucidated. Neutrophils make reactive oxidant species (ROS). ROS are implicated in the pathogenesis of vasospasm and are believed to contribute to oxidative injury and nitric oxide (NO) depletion. These are believed to contribute to the blood vessel dysfunction in vasospasm. We proposal to test the hypothesisthat neutrophil accumulation in the subarachnoid space and selective increase in neutrophil-derived molecular markers of oxidative pathways will correlate with the occurrence of vasospasm after subarachnoid hemorrhage. We plan to investigate this by developing two specific aims: 1) We will establish the relationship between neutrophil enrichment in the subarachnoid space, stable molecular markers of distinct oxidative pathways and vasospasm; and 2) We will determine the implications of neutrophil depletion, activation, the inactivation of two neutrophil enzymes, NADPH oxidase and MPO, and the inactivation of the chemokines CXCR2 on the development of vasospasm in a murine model. There is no effective treatment of vasospasm. This proposal will lead to a better understanding of the pathways by which neutrophil infiltration and action may lead to vasospasm. This is relevant because neutrophils and neutrophil chemokines are potential targets for pharmacologic therapy to prevent or treat vasospasm. This proposal and the educational components included form the basis for Dr. Provencio to develop into an independent physician-scientist.

在美国，蛛网膜下腔出血是导致中风的第三大原因，但占了50%