Hypoxia/Reoxygenation Effects on the Blood-brain Barrier

缺氧/复氧对血脑屏障的影响

• 批准号: 6529140
• 负责人: Karen S Mark
• 金额: $ 3.94万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6529140
• 关键词: blood brain barrier; carbon; cerebral ischemia /hypoxia; cytoskeletal proteins; fluorescence microscopy; gene expression; hypoxia; immunoprecipitation; nitric oxide; phosphorylation; protein localization; radionuclides; stroke; tight junctions; tissue /cell culture; vascular endothelium permeability; western blottings

DESCRIPTION (provided by applicant): Stroke is the leading cause of death and long-term disability in the United States, yet little is understood regarding how an ischemic event induces a breakdown and increased permeability of the blood-brain barrier (BBB). Although hypoxia associated with stroke has been reported to cause increased BBB permeability, effects of re-oxygenation on brain endothelial cells following a hypoxic insult remain unclear. Tbe hYpothesis of this proposal is that hvpoxia induces significant alterations in expression and localization of junctional and cYtoskeletal proteins leading to increased BBB perrneability and tbese effects are reduced during re-oxygenation. This proposal expands on previous work of hypoxic insult to the BBB by focusing on functional and biochemical alterations in brain microvessel endothelial cells during hypoxia and re-oxygenation. Changes in BBB permeability, alterations in cytoarchitecture (i.e., expression of cytoskeletal and junctional proteinsl, and changes in phosphorylation states/ localization patterns will be examined using an in vitro BBB model following hypoxia/re-oxygenation treatment. Together, data from this project will demonstrate how alterations in the cytoskeletal framework and junctional proteins are related to functional changes (i.e., increased paracellular permeability) that occur during hypoxia and re-oxygenation phases of ischemic stroke.

描述（由申请人提供）： 中风是美国人死亡和长期残疾的主要原因。 然而，关于缺血性事件如何诱导脑缺血， 血脑屏障（BBB）的破坏和渗透性增加。虽然 据报道，与中风相关的缺氧会导致BBB增加 渗透性，再给氧对脑内皮细胞的影响， 缺氧损伤仍不清楚。这一建议的假设是， 诱导连接蛋白的表达和定位发生显著改变， 和细胞骨架蛋白，导致BBB通透性增加， 在再氧合期间效果降低。 该建议扩展了以前的工作，缺氧损伤血脑屏障，重点是 对脑微血管内皮细胞功能和生化改变的影响 细胞缺氧和复氧。BBB通透性的变化， 细胞结构的改变（即，表达细胞骨架和 连接蛋白l和磷酸化状态/定位的变化 将使用体外BBB模型检查模式， 缺氧/复氧处理。总之，该项目的数据将 展示了细胞骨架和连接结构的改变 蛋白质与功能变化有关（即，细胞旁增加 渗透性），发生在缺血缺氧和复氧阶段 中风