OXIDATIVE METABOLISM

氧化代谢

• 批准号: 6318355
• 负责人: ROBERT C. VANNUCCI
• 金额: $ 15.82万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6318355
• 关键词: Krebs' cycle; acid base balance; autoradiography; bioenergetics; brain circulation; brain injury; brain metabolism; carbon dioxide; cerebral ischemia /hypoxia; glycolysis; histopathology; immature animal; laboratory rat; lactates; neuroprotectants; nuclear magnetic resonance spectroscopy; perinatal

The overall objective of this project is to elucidate biochemical and physiologic mechanisms responsible for perinatal hypoxic-ischemic brain damage and to develop strategies which will arrest or retard these processes. Specific aims include: 1) to characterize those critical cellular metabolic events which precede or parallel the evolution of include: 1) to characterize those critical cellular metabolic events which precede or parallel the evolution of identifiable lesions resulting from cerebral hypoxia-ischemia in the immature rat; 2) to investigate the apparent identifiable lesions resulting from cerebral hypoxia-ischemia in the immature rat; 2) to investigate the apparent delayed or secondary energy failure which occurs during recovery from hypoxia-ischemia in the immature rat and to determine whether or not the phenomenon causes or contributes to brain damage; 3) to investigate further the beneficial effect of carbon dioxide on hypoxic-ischemic brain damage in the developing rat; and 4) to investigate further the influence of alterations in glucose and lactate homeostasis on hypoxic-ischemic brain damage in the developing rat and to identify those mechanisms whereby glucose exerts a beneficial or harmful effect on neuropathologic outcome. To accomplish these goals, the Principal Investigator will use the following analytical techniques: 1) the iodo-{14C}-antipyrine technique to measure cerebral blood flow; 2) the 2-deoxy-[14C]-glucose and [4C]-glucose techniques to measure cerebral glucose utilization; 3) in vivo analysis of glycolytic and Krebs cycle intermediates and high-energy phosphates reserves in brain tissues; 4) determination of cerebral energy utilization, intracellular pH, and the redox state of brain tissue; 5) regional analysis of calcium and sodium uptake and turnover by brain; 6) histopathologic analysis of brain specimens; and 7) MR spectroscopy.

该项目的总体目标是阐明围产期缺氧缺血性脑损伤的生化和生理机制，并制定策略，将逮捕或延缓这些过程。具体目标包括：1）表征那些先于或平行发展的关键细胞代谢事件，包括：1）表征那些先于或平行于未成熟大鼠中由脑缺氧-缺血引起的可识别损伤发展的关键细胞代谢事件; 2）研究未成熟大鼠中由脑缺氧-缺血引起的明显可识别损伤; 2）研究在未成熟大鼠从缺氧-缺血恢复期间发生的明显延迟或二次能量衰竭，并确定该现象是否引起或促成脑损伤; 3）进一步研究二氧化碳对发育中大鼠缺氧-缺血性脑损伤的有益作用; 4）进一步研究葡萄糖和乳酸稳态的改变对发育中大鼠缺氧缺血性脑损伤的影响，并确定葡萄糖对神经病理结果产生有益或有害影响的机制。为了实现这些目标，主要研究者将使用以下分析技术：1）碘-{14 C}-安替比林技术测量脑血流量; 2）2-脱氧-[14 C]-葡萄糖和[4 C]-葡萄糖技术测量脑葡萄糖利用率; 3）糖酵解和克雷布斯循环中间体和脑组织中高能磷酸盐储备的体内分析; 4）脑能量利用、细胞内pH和脑组织的氧化还原状态的测定; 5）脑的钙和钠摄取和周转的区域分析; 6）脑标本的组织病理学分析;和7）MR波谱。