CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS

描述：这是竞争性续订的第二次修订 应用于研究缺氧性脑损伤的基本机制， 新生猪实验旨在研究特定的 脑细胞损伤的细胞学机制 缺氧程度与活性和结构的改变 N-甲基-D-天冬氨酸（NMDA）受体-离子通道复合物， 组织病理学改变。 研究人员假设， 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 补助金申请的一个方面。 程度的确定 缺氧在体内将通过连续监测脑 利用31-P核磁共振研究高能磷酸盐储量 光谱以及大脑皮层氧的测定 通过磷光的氧依赖性猝灭的压力。 细胞膜脂质过氧化、钠/钾- ATP酶活性和氧自由基的存在将被使用 作为脑细胞损伤的指标。将进行光学显微镜检查 评估从以下恢复48小时时的组织病理学变化： 缺氧 所有实验将在新生猪中进行， 探讨：1）定量组织缺氧与 以及识别和调节位点的结构， 受体/离子通道复合物的激活; 2） 缺氧对NMDA介导的钙离子向突触神经小体内流的影响; 3） 脂质过氧化反应的发生与 NMDA的识别和调节位点的改变 4）定量组织缺氧与 释放特定的单胺类和氨基酸类神经递质; 5）增加氨基酸和单胺释放的作用 缺氧时神经递质对脑细胞活性的影响 钠/钾-ATP酶和NMDA活性的改变。 实验将研究低血糖的增强作用 缺氧时NMDA受体活性和细胞膜 功能 所提议的实验将使用良好- 确定配体结合的既定技术， 酶动力学，微透析，HPLC，组织病理学方法和 他人 有人建议，实验的结果将 为脑细胞膜功能提供了新的见解， 更好地理解缺氧的基本机制 新生儿的神经元损伤。

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.