REGIONAL BRAIN METABOLISM IN HEPATIC COMA

这项研究的目的是确定一些生理和 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， 可以判断治疗措施。 仔细表征大鼠， 门体分流术将被用作慢性脑病的模型。 大脑必需营养物质的供应由血浆决定 浓度和便于其通过的运输系统 穿过血脑屏障 在正常动物中，血脑屏障 在供应和需求之间保持微妙的平衡，但 门体分流，几个渗透性特征 运输系统明显改变。 据信， 脑源性脑病的病因学意义 接受了过量的某些营养，但可能几乎没有其他营养。 需要研究的必需营养素包括中性和碱性氨基 酸、葡萄糖、胆碱、嘌呤和核苷。 区域交通具体变化的时间进程将是 测定 结果将与神经功能的变化进行比较， 通过使用[2- 14 C]葡萄糖测量葡萄糖利用率来确定， 整个大脑或结构水平。 血脑屏障改变的机制可能与 NH 4+代谢为谷氨酰胺。 这将在体内进行研究， 操纵血液NH 4浓度和脑谷氨酰胺含量， 慢性和急性实验。 碱性氨基酸流入的减少是如此极端， 可能会延迟。 这种可能性将在整个大脑和 通过测定蛋白质合成速率来确定单个结构。

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.