Dynamic MRI and MRS studies of focal neural activation

描述(由申请人提供)： 与电活动改变对血流动力学和葡萄糖/氧代谢的影响相比，在神经胶质水平上大脑激活的神经化学、神经能量和代谢基础在体内的研究还不够深入，我们的长期目标是获得对大脑碳水化合物代谢的全面评估，因为它与完整大脑中大脑活动的增加和神经元/胶质细胞的划分有关。我们的中心假设是谷氨酸神经传递只占大脑葡萄糖总消耗量的一小部分，苹果酸-天冬氨酸穿梭是大脑葡萄糖氧化代谢的主要速率决定机制。总体战略是使用一种新兴的新工具--超高磁场下最先进的13C和1H核磁共振波谱，结合功能性磁共振成像，测量大鼠、冬眠松鼠和人类的胶质和神经元能量代谢、苹果酸-天冬氨酸穿梭(MAS)活动、脑糖原代谢和葡萄糖运输。该项目代表着我们正在进行的努力的继续，其结果将是在细胞水平上对体内大脑功能的神经化学基础提供前所未有的全面了解，并有可能在许多涉及谷氨酸的神经退行性疾病和其他大脑疾病的结构变化明显之前很久就确定疾病进展的特征。

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.