REGIONAL BRAIN METABOLISM IN HEPATIC COMA

大脑功能和意识水平发生改变 在某些代谢性疾病中， 底物和激素影响的合成和营业额 脑神经传递素 病理生理机制 负责大脑功能障碍，这些代谢 脑病仍有待澄清。 发生了几 近年来的重大技术进步， 这些疾病的研究取得进一步进展。 电流 代谢性脑病病因学的假说 往往只关注疾病的孤立方面。 但 代谢性脑病的多因素性质表明， 阐明其病因的最有效方法是 整合了已经描述的各种异常。 神经递质代谢改变与 分布，受体密度和分布，蛋白质合成， 和大脑功能，在疾病的不同阶段， 揭示了脑病发展的关键步骤， 可能仍然模糊的研究中的单一变量在孤立的 时间点。 因此，本提案的目标将 强调以下几个方面： 生物化学、生理和结构变化， 重要的是引起代谢过程中意识的改变 疾病，然后确定任何病因因素 常见于各种代谢性脑病（例如，肝脏， 尿毒症和糖尿病）。 将研究由门体分流引起的脑病 先 神经递质的局部定位及其对神经元的影响 代谢将与代谢的功能阶段有关， 脑病 将通过以下方式测量局部葡萄糖使用情况： 定量放射自显影，并用作脑 功能 主要神经递质的局部脑含量， 采用高效液相色谱法测定其代谢产物 层析 将评估其受体的分布 通过定量放射自显影。 的测量方法 将制定区域氨代谢率， 验证. 血液和大脑中的氨基酸谱， 影响神经递质代谢，将测量 同时。 随后的研究将扩展到 尿毒症和糖尿病脑病。

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.