High-Speed Assays for Neuromessengers Involved in Stroke

中风神经信使的高速检测

• 批准号: 6678526
• 负责人: MICHAEL T BOWSER
• 金额: $ 28.48万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6678526
• 关键词: antioxidants; biological signal transduction; capillary electrophoresis; glutamates; histology; ischemia; laboratory rat; microdialysis; neurochemistry; nitric oxide; pharmacokinetics; reperfusion; serine; stroke; technology /technique development; tissue /cell culture; zinc

Toxic levels of glutamate released during ischemia have been implicated in the damage caused by stroke. Unfortunately, drugs that mediate the effect of glutamate have proven ineffective or cause unacceptable side effects. Current research is moving towards investigating a number of neuromessengers involved in glutamate signaling including Zn2+, D-serine and nitric oxide. Developing treatments for stroke based on these neuromessengers has been hampered by our limited understanding of their function in vivo. Currently there are no methods for measuring the dynamics of Zn2+, D-serine and nitric oxide in vivo on a time scale of seconds. We propose designing online capillary electrophoresis-microdialysis assays for Zn2+, D-serine and nitric oxide capable of making measurements every 10 seconds, a 120-fold improvement over existing techniques. These assays will allow a detailed pharmacological study of the function Zn2+, D-serine and nitric oxide play in vivo. Tissue (salamander retina) and single cell models (neuron and gila) will also be studied to compare different levels of complexity. The dynamics of Zn2+, D-serine and nitric oxide will be measured during ischemia and reperfusion for the first time. It is hypothesized that toxic concentrations of Zn2+ and nitric oxide are released during ischemia. Understanding what happens in the brain chemically during ischemia is cdtical considering that most of the damage caused by stroke is thought to be chemical in origin. We will use the high temporal resolution assays for glutamate, Zn2+, D-serine and nitric oxide to test the effect of several proposed preventative stroke treatments. Classes of compounds that will be tested include blood thinners (aspirin, t-PA), anaerobic energy sources (creatine, arginine), antioxidants (vitamins C and E) and metal chelators (EDTA).

脑缺血时释放的谷氨酸毒性水平与脑卒中造成的损伤有关。不幸的是，调节谷氨酸作用的药物已被证明无效或