AMINO ACID TRANSPORT IN HYPERAMMONEMIC CONDITIONS

高氨条件下的氨基酸转运

• 批准号: 3432629
• 负责人: JAMES E OLSON
• 金额: $ 2.38万
• 依托单位: WRIGHT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3432629
• 关键词: aminoacid transport; basal ganglia; blood brain barrier; body fluid osmolarity; brain edema; capillary; carbamoyl phosphate synthetase deficiency; cell morphology; disease /disorder model; electronic stimulator; hepatic coma /encephalopathy; laboratory rat; liver failure

Hepatic encephalopathy (HE) is a complex medical condition involving an acute degeneration in mental status leading to coma and death if untreated. Cerebral edema and elevated intracranial pressure is a consistent finding in HE. Morphologically cerebral astroglial cells are swollen with little change in extracellular volume, characteristics of cytotoxic cerebral edema. Considerable alterations occur in blood chemistry during HE including increased concentrations of ammonia, fatty acids and a variety of aromatic amino acids. Elevated concentrations of these compounds in the serum may initiate a variety of metabolic changes in the brain during HE including alterations in blood flow, energy metabolism, and blood-brain barrier transport. Each of these metabolic perturbations may contribute to the development of cerebral edema. This research project will investigate the role that amino acid transport plays in the development of regional brain edema and in the regulation of brain water content during HE. Based on preliminary studies performed by the Principal Investigator and Foreign Collaborator, we shall measure transport of amino acids which may serve as osmoeffectors in the brain. Transport will be measured in situ across the blood-brain barrier and in preparations of brain tissue slices and capillaries. We also shall determine whether this transport is altered in encephalopathic animals during volume regulation imposed by alterations in perfusing medium osmolality. These experiments will contribute to the goals of the parent grant by exploring the mechanisms of brain edema development in HE and the role of amino acid transport in brain water and cellular volume regulation. Future studies can use these results to determine whether serum factor(s) present in HE disposes the brain to develop edema by altering transport.

肝脑病（He）是一种复杂的医疗状况，涉及 如果心理状态急性变性，导致昏迷和死亡 未经处理。 脑水肿和颅内压升高是 他的一致发现。 形态学上脑星形胶质细胞是 肿胀，细胞外体积几乎没有变化，特征的特征 细胞毒性脑水肿。 血液发生了很大的改变 化学在他期间包括氨，脂肪的浓度增加 酸和多种芳香氨基酸。 浓度升高 血清中的这些化合物可能会引发多种代谢变化 在他的大脑中，包括血流的改变，能量 代谢和血脑屏障运输。 这些代谢中的每一个 扰动可能有助于大脑水肿的发展。 这 研究项目将调查氨基酸转运的作用 在区域大脑水肿的发展和调节中发挥作用 他在他期间的脑含量。 基于进行的初步研究 由首席调查员和外国合作者，我们将衡量 可以用作大脑中的osmoeffector的氨基酸的转运。 运输将在血脑屏障上进行原位测量 脑组织切片和毛细血管的制剂。 我们也将 确定脑病动物中是否改变了这种运输 在体积调节期间，通过改变培养基的改变 渗透压。 这些实验将为父母赠款的目标做出贡献 探索HE中脑水肿发展的机制和角色 在脑水中的氨基酸转运和细胞体积调节。 未来的研究可以使用这些结果来确定血清因子是否是否 他在他中存在通过改变运输来消除大脑以发展水肿。