Dynamic MRI and MRS studies of focal neural activation

局灶性神经激活的动态 MRI 和 MRS 研究

• 批准号: 6701757
• 负责人: ROLF GRUETTER
• 金额: $ 34.61万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-10 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6701757
• 关键词: Krebs' cycle; aspartate; beta hydroxybutyrate; bioenergetics; bioimaging /biomedical imaging; brain circulation; brain metabolism; clinical research; functional magnetic resonance imaging; glia; glucose metabolism; glucose transport; glycogen; glycogenolysis; human subject; laboratory rat; malates; neural transmission; neurochemistry; neurons; nuclear magnetic resonance spectroscopy; phosphorylases; pyruvate dehydrogenase; squirrel

DESCRIPTION (provided by applicant): In contrast to the hemodynamic and glucose/oxygen metabolic consequences of altered electrical activity, the neurochemical, neuroenergetic and metabolic basis of brain activation at the neuroglial level is not as well researched in vivo, It is our long-term objective to obtain a comprehensive assessment of cerebral carbohydrate metabolism as it relates to increased brain activity and neuronal/glial compartmentation in the intact brain. Our central hypothesis is that glutamate neurotransmission represents a fraction of total brain glucose consumption and that the malate-aspartate shuttle is a major rate-determining mechanism in oxidative brain glucose metabolism. The overall strategy is to measure glial and neuronal energy metabolism, malate-aspartate shuttle (MAS) activity, brain glycogen metabolism and glucose transport in rats, hibernating squirrels and humans using an emerging new tool, state-of-the-art 13C and 1H NMR spectroscopy at ultra-high magnetic fields, combined with functional MR imaging. The project represents the continuation of our ongoing effort, the outcome of which will be to provide an unprecedented comprehensive understanding of the neurochemical basis of brain function in vivo at the cellular level, with the potential to characterize disease progression long before structural changes are evident in many neurodegenerative and other diseases of the brain, where glutamate has been implicated.

描述（由申请人提供）： 与电活动改变的血流动力学和葡萄糖/氧代谢后果相比，神经胶质细胞水平的大脑激活的神经化学、神经能量和代谢基础在体内研究还不够充分，我们的长期目标是获得全面的评估脑碳水化合物代谢的影响，因为它与完整大脑中大脑活动的增加和神经元/神经胶质区划有关。我们的中心假设是，谷氨酸神经传递仅占脑葡萄糖消耗总量的一小部分，而苹果酸-天冬氨酸穿梭是氧化脑葡萄糖代谢的主要速率决定机制。总体策略是使用新兴工具（最先进的 13C 和 1H）测量大鼠、冬眠松鼠和人类的神经胶质和神经元能量代谢、苹果酸-天冬氨酸穿梭 (MAS) 活性、脑糖原代谢和葡萄糖转运超高磁场下的核磁共振波谱与功能性核磁共振成像相结合。该项目代表了我们持续努力的延续，其结果将是在细胞水平上对体内脑功能的神经化学基础提供前所未有的全面了解，并有可能在结构变化明显之前就描述疾病进展的特征。许多神经退行性疾病和其他大脑疾病都与谷氨酸有关。