REGIONAL BRAIN METABOLISM IN HEPATIC COMA

肝昏迷时的区域脑代谢

• 批准号: 3396857
• 负责人: RICHARD A HAWKINS
• 金额: $ 23.94万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3396857
• 关键词: aminoacid metabolism; aminoacid transport; ammonia; autoradiography; blood brain barrier; brain metabolism; detoxification; diabetic neuropathy; glucose metabolism; hepatic coma /encephalopathy; high performance liquid chromatography; laboratory rat; neuroanatomy; neurochemistry; neurophysiology; neurotransmitter metabolism; protein biosynthesis; uremias

Alterations in cerebral function and levels of consciousness occur in certain metabolic diseases where changes in circulating substrates and hormones influence the synthesis and turnover of brain neurotransmitters. The pathophysiologic mechanisms responsible for cerebral dysfunction in these metabolic encephalopathies remain to be clarified. There have been several important technical advances in recent years which will permit further progress in the study of these diseases. Current hypotheses of the etiology of metabolic encephalopathy have tended to focus only on isolated facets of the disease. But the multifactorial nature of metabolic encephalopathy suggests that the most productive approach to elucidating its etiology will be to integrate the various abnormalities which have been described. Correlation of alterations in neurotransmitter metabolism and distribution, receptor density and distribution, protein synthesis, and cerebral function, at different stages of the disease may reveal crucial steps in the development of encephalopathy that might remain obscure in studies of single variables at isolated time points. Accordingly, the goals of this proposal will emphasize the following aspects: the identification of those biochemical, physiologic and structural changes which are important in causing alterations in consciousness in metabolic disease, followed by the determination of any etiologic factors common to various metabolic encephalopathies (e.g., hepatic, uremic and diabetic). Encephalopathy caused by portal-systemic shunting will be studied first. Regional localization of neurotransmitters and their metabolism will be related to the functional stages of metabolic encephalopathy. Regional glucose use will be measured by quantitative autoradiography and used as an index of cerebral function. Regional brain content of major neurotransmitters and their metabolites will be determined by high performance liquid chromatography. Distribution of their receptors will be evaluated by quantitative autoradiography. A method for measuring the regional rate of ammonia metabolism will be developed and validated. Amino acid profiles in blood and brain, which may effect neurotransmitter metabolism, will be measured concurrently. Subsequently studies will be extended to models of uremic and diabetic encephalopathy.

大脑功能和意识水平发生改变 在某些代谢性疾病中，循环系统发生变化 底物和激素影响合成和周转 大脑神经递质。 病理生理机制 这些代谢功能障碍是造成脑功能障碍的原因 脑病仍有待澄清。 已经有好几个 近年来的重要技术进步将允许 这些疾病的研究取得进一步进展。 当前的 代谢性脑病病因学的假设 倾向于只关注疾病的孤立方面。 但是 代谢性脑病的多因素性质表明 阐明其病因最有效的方法是 整合已描述的各种异常。 神经递质代谢变化与 分布、受体密度和分布、蛋白质合成、 和脑功能，在疾病的不同阶段可能 揭示脑病发展的关键步骤 在孤立的单个变量的研究中可能仍然模糊 时间点。 因此，本提案的目标将 强调以下几个方面： 识别那些 生化、生理和结构变化 对于引起新陈代谢中意识的改变很重要 疾病，然后确定任何病因因素 常见于各种代谢性脑病（例如肝性、 尿毒症和糖尿病）。 将研究门体分流引起的脑病 第一的。 神经递质的区域定位及其作用 新陈代谢将与代谢的功能阶段有关 脑病。 区域葡萄糖使用量将通过以下方式测量 定量放射自显影术并用作脑的指标 功能。 主要神经递质的区域脑含量和 他们的代谢物将通过高性能液体测定 色谱法。 将评估其受体的分布 通过定量放射自显影。 一种测量方法 将开发区域氨代谢率 已验证。 血液和大脑中的氨基酸谱，这可能 影响神经递质代谢，将被测量 同时。 随后的研究将扩展到模型 尿毒症和糖尿病脑病。