REGIONAL BRAIN METABOLISM IN HEPATIC COMA

这项研究的目标是定义一些生理和 慢性肝性脑病期间发生的生化变化。 这是朝着确定客观标准迈出的必要的第一步 治疗措施是可以判断的。仔细地描述了老鼠的特征 门体分流将被用作慢性脑病的模型。 脑部必需营养素的供应由血浆决定。 集中度和便利其通过的运输系统 穿过血脑屏障。在正常动物中，血脑屏障 在供需之间调解微妙的平衡，但遵循 门体分流，几种通透性的特点 交通系统发生了明显的变化。据信，这是 脑源性疾病发生发展的病因学意义 接受一些多余的营养，但可能几乎缺乏其他营养。 在需要研究的必需营养素中有中性和碱性氨基酸。 酸、葡萄糖、胆碱、嘌呤和核苷。 区域运输的具体变化的时间进程将是 下定决心。结果将与神经功能的变化进行比较，如 通过使用[2-14C]葡萄糖在任一种情况下测量葡萄糖利用率来确定 整个大脑或结构层面。 血脑屏障改变的机制可能与 NH4+代谢为谷氨酰胺。这将在体内进行研究，通过 控制血液中NH4浓度和脑内谷氨酰胺含量 慢性和急性实验。 碱性氨基酸内流的减少是如此极端，以至于蛋白质合成 可能是智障。这种可能性将在整个大脑和 通过测定蛋白质合成的速率来确定个体结构。

The goal of this research is to define some of the physiological and biochemical changes which occur during chronic hepatic encephalopathy. This is a necessary first step toward defining objective criteria by which therapeutic measures can be judged. Carefully characterized rats with portal-systemic shunts will be used as a model of chronic encephalopathy. The supply of essential nutrients to brain is determined by the plasma concentrations and the transport systems which facilitate their passage across the blood-brain barrier. In normal animals, the blood-brain barrier mediates a delicate balance between supply and need, but following portal-systemic shunting, the permeability characteristics of several transport systems are markedly altered. This is believed to be of etiologic significance to the development of encephalopathy since brain receives an excess of some nutrients but may be almost starved of others. Among the essential nutrients to be studied are neutral and basic amino acids, glucose, choline, purines and nucleosides. The time course of specific changes in regional transport will be determined. The results will be compared to changes in neural function as determined by measuring glucose utilization using [2-14C]glucose in either whole brain or at the structural level. The mechanism of the blood-brain barrier changes may be closely related to metabolism of NH4+ to glutamine. This will be studied in vivo by manipulating blood NH4 concentrations and cerebral glutamine content in chronic and acute experiments. Reduction of basic amino acid influx is so extreme that protein synthesis may be retarded. This possibility will be examined in whole brain and in individual structures by determination of the rate of protein synthesis.