BLOOD TO BRAIN SODIUM TRANSPORT

血液到大脑的钠转运

• 批准号: 3407860
• 负责人: A LORRIS BETZ
• 金额: $ 19.48万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3407860
• 关键词: adenosinetriphosphatase; blood brain barrier; brain circulation; brain edema; cerebral ischemia /hypoxia; hypoglycemia; ion transport; membrane transport proteins; potassium; sodium

DESCRIPTION: (Investigator's abstract): The goal of this proposal is to determine the mechanisms responsible for the transport of ions across the blood-brain barrier (BBB) and to understand how these processes are regulated. The BBB is formed by capillary endothelial cells which control the flux of solutes between blood and brain, thus regulating the composition of the brain's interstitial fluid. To accomplish this task, the capillary endothelium acts similarly to an epithelium actively transporting ions and water across its cells. The ion transporters are likely to be important for maintaining the Na and K homeostasis with the brain for optimal neuronal activity. When this mechanism is disrupted, neuronal dysfunction and/or brain edema results. In the previous grant period, the investigator showed that the blood to brain Na transport plays an important role in the development of brain edema during ischemia. These results led the investigator to postulate that the concentration of K in the brain interstitial fluid (Ke) is an important modulator for Na transport into the brain. An increase in Ke would increase K extrusion into the capillaries and accelerate the flux of Na from the blood into the brain. The present proposal is an effort to test this hypothesis by simultaneously measuring Ke (with K-sensitive electrodes), Na and CI transport under three conditions where Ke is elevated: a) reperfusion following complete cerebral ischemia; b) incomplete cerebral ischemia and c) severe hypoglycemia. He will investigate the importance of Na, K-ATPase, sodium channels and sodium co-transport systems in the blood to brain Na transport. For this purpose, he will use conditions in which the capillary Na, K-ATPase system is up- or down-regulated and by administering potent inhibitors of the Na channels or Na-CI transport.

描述：（研究者的摘要）：该提议的目的是 确定负责离子在整个整个跨越的机制 血脑屏障（BBB），并了解这些过程是如何的 受监管。 BBB由控制的毛细管内皮细胞形成 血液和大脑之间溶质的通量，从而调节 大脑间质液的组成。 为了完成这项任务， 毛细管内皮的作用类似于上皮的作用 在其细胞上运输离子和水。 离子转运蛋白是 对于维持Na和K的稳态可能很重要 最佳神经元活性的大脑。 当这种机制破坏时， 神经元功能障碍和/或脑水肿结果。 在上一个赠款期间，调查人员表明血液流向 脑NA运输在大脑发展中起重要作用 缺血期间的水肿。 这些结果导致调查员假设 脑间隙液（KE）中K的浓度是 NA转运到大脑的重要调节剂。 KE的增加 会增加K挤出到毛细管中，并加速 NA从血液进入大脑。 目前的建议是通过同时检验该假设的努力 测量KE（带有K敏感电极），Na和Ci在三个下运输 KE升高的条件：a）重新灌注后完成 脑缺血； b）脑缺血不完全，c）严重 低血糖。 他将研究Na，K-ATPase，钠的重要性 血液中的通道和钠共同传输系统 运输。 为此，他将使用毛细管的条件 Na，K-ATPase系统是向上或下调的，并通过管理有效 Na通道或Na-CI转运的抑制剂。