CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS

描述：这是竞争续订的第二次修订 在低氧性脑损伤基本机制研究中的应用 新生的猪。实验的设计是为了研究特定的 仔猪脑细胞损伤的相关细胞机制 低氧程度与活性和结构的变化 N-甲基-D-天冬氨酸(NMDA)受体-离子通道复合体和 组织病理学改变。调查人员假设 缺氧的严重程度会对功能产生特定的影响 可能还有NMDA受体的结构，这是一种独特的 在拨款申请方面。程度的确定 通过对大脑的持续监测，将实现体内缺氧 高能磷酸盐储量的31P核磁共振研究 光谱学和大脑皮层氧含量的测定 压力依赖于氧猝灭的磷光。 细胞膜脂质过氧化、钠/钾测定 将使用ATPase活性和氧自由基的存在 作为脑细胞损伤的指标。将进行光学显微镜检查 在恢复48小时后评估组织病理学变化。 缺氧。所有实验都将在新生猪身上进行，以 研究：1)定量组织缺氧之间的关系 以及识别和调控位点的结构以及 受体/离子通道复合体的激活；2) 低氧对NMDA介导的钙内流至突触神经体的影响 脂质过氧化反应的发生与组织病理学改变的关系 NMDA的识别和调控位点的变化 4)定量组织缺氧与组织缺氧的关系。 释放特定的单胺和氨基酸类神经递质； 5)增加氨基酸和单胺的释放 低氧时神经递质对脑细胞活动的影响 钠/钾-ATPase与NMDA活性的变化 实验将研究低血糖的增强作用。 低氧对NMDA受体活性和细胞膜的影响 功能。拟议的实验将使用井- 已建立的测定配基结合和 酶动力学、微渗析、高效液相、组织病理学方法和 其他。据建议，这些实验的结果将 为脑细胞膜功能提供新的见解，并将引领 以更好地了解导致缺氧的基本机制 新生儿的神经细胞损伤。

DESCRIPTION:This is the second revision of a competitive renewal application to study basic mechanisms of hypoxic brain damage in newborn pigs. Experiments were designed to investigate specific cellular mechanisms of brain cell injury in the piglet by correlating the degree of hypoxia with alterations in the activity and structure of the N-methyl-D-aspartate (NMDA) receptor-ion channel complex and tissue histopathologic changes. The investigators hypothesize that the severity of hypoxia will have a specific impact on the function and possibly the structure of the NMDA receptor, which is a unique aspect of the grant application. The determination of the degree of hypoxia in vivo will be achieved by the continuous monitoring of brain high energy phosphate reserves using 31-P nuclear magnetic resonance spectroscopy as well as the determination of cerebral cortical oxygen pressure by oxygen- dependent quenching of phosphorescence. Measurements of cell membrane lipid peroxidation, sodium/potassium- ATPase activity and the presence of oxygen free radicals will be used as indices of brain cell injury. Light microscopy will be performed to assess histopathologic changes at 48 hours of recovery from hypoxia. All experiments will be conducted in newborn pigs to investigate: 1) the relationship between quantitative tissue hypoxia and the structure of the recognition and modulatory sites and the activation of the receptor/ion channel complex; 2) the effect of hypoxia on NMDA-mediated influx of calcium into synaptoneurosomes; 3) the relationship between the occurrence of lipid peroxidation and alterations in the recognition and modulatory sites of the NMDA receptor; 4) the relationship between quantitative tissue hypoxia and the release of specific monoamines and amino acid neurotransmitters; and 5) the effect of increased release of amino acid and monoamine neurotransmitters during hypoxia on the activity of brain cell sodium/potassium-ATPase and alterations in NMDA activity.Additional experiments will investigate the potentiating effect of hypoglycemia during hypoxia on both NMDA receptor activity and cell membrane function. The proposed experiments will be performed using well- established techniques for the determination of ligand binding and enzyme kinetics, microdialysis, HPLC, histopathologic methods and others. It is proposed that the findings of the experiments will provide new insights into brain cell membrane function and will lead to a better understanding of basic mechanisms contributing to hypoxic neuronal injury in the newborn human infant.