HUMAN CEREBRAL GABA METABOLISM STUDIED IN VIVO WITH NMR

描述（研究者摘要）：谷氨酸是主要的 γ-氨基丁酸（GABA）主要抑制 哺乳动物大脑和人类大脑皮层中的神经递质。动物模型 一致表明，GABA突触功能是 在癫痫发作的国家减少。对动物的广泛研究表明， GABA释放和代谢的变化可能在 在癫痫发作活动的起源和传播中的作用。虽然可以 推断治疗中报告的临床获益 癫痫与脑的升高有关并可归因于脑的升高 GABA，证据表明大脑GABA水平的变化，在男人是 缺乏核磁共振波谱学的新进展 （NMRS）允许第一次非侵入性测量大脑 动物和人的GABA：GABA合成和catalysis的研究 人类大脑皮层将进一步了解这种重要的抑制 神经递质在人类健康和疾病中的作用我们建议研究 非癫痫患者脑内GABA和谷氨酸水平的变化 志愿者和癫痫患者。氨己烯酸（γ-乙烯基-γ-氨基 丁酸），一种GABA-转氨酶抑制剂，是最重要的 正在开发的有前途的抗癫痫新药。我们建议 研究脑内GABA和谷氨酸水平的变化， 癫痫作为氨己烯酸给药剂量和时间的函数 使用NIRRS。该研究有四个目标：测量体内大脑 非癫痫和癫痫受试者中的GABA和谷氨酸水平， 测量用以下药物治疗的癫痫受试者的脑GABA水平： 标准剂量和高剂量氨己烯酸，以测量大脑GABA 癫痫受试者开始治疗前和治疗后的水平 氨己烯酸治疗，并比较GABA积累率 单剂量氨己烯酸后，GABA周转率 在大鼠模型中长期施用氨己烯酸之前和之后 使用13 C标记的葡萄糖。

DESCRIPTION (Investigator's Abstract): Glutamate is the major excitatory and y-aminobutyric acid (GABA) the major inhibitory neurotransmitter in mammalian brain and human cortex. Animal models of epilepsy consistently indicate that GABA synaptic function is decreased in seizure states. Extensive studies in animals have shown that changes in GABA release and metabolism may play an important role in the origin and spread of seizure activity. Although it can be inferred that the clinical benefit reported in the treatment of epilepsy is associated with and attributable to elevation of brain GABA, evidence to show changes in brain GABA levels in man is lacking. Recent advances in nuclear magnetic resonance spectroscopy (NMRS) have permitted the first non-invasive measurements of cerebral GABA in animals and man. Studies of GABA synthesis and catabolism in human cortex will further understanding of this important inhibitory neurotransmitter in human health and disease. We propose to study changes in cerebral GABA and glutamate levels in non-epileptic volunteers and patients with epilepsy. Vigabatrin (y-vinyl-y-amino butyric acid), a GABA- transaminase inhibitor, is one of the most promising new anti-epileptic drugs under development. We propose to study changes in cerebral GABA and glutamate levels in patients with epilepsy as a function of dose and time of vigabatrin administration using NlVlRS. The study has four goals: To measure in vivo cerebral GABA and glutamate levels in non-epileptic and epileptic subjects, to measure cerebral GABA levels in epileptic subjects treated with standard dose and high dose vigabatrin, to measure cerebral GABA levels of epileptic subjects before and after initiation of vigabatrin therapy, and to compare the rate of GABA accumulation following a single dose of vigabatrin with the rate of GABA turnover before and after chronic administration of vigabatrin in a rat model using 13C-labeled glucose.