NEWBORN CEREBRAL HEMORRHAGE AND ARACHIDONATE METABOLITES

新生儿脑出血和花生四烯酸代谢物

• 批准号: 2220718
• 负责人: CHARLES W. LEFFLER
• 金额: $ 19.21万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-16 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2220718
• 关键词: arachidonate; cerebral hemorrhage; electron microscopy; fatty acid metabolism; histopathology; leukotrienes; microcirculation; newborn animals; prostaglandins; radiation detector; radioimmunoassay; radionuclides; radiotracer; spectrometry; statistical service /center; superoxide dismutase; superoxides; swine; vasoconstriction

These studies are designed to address the overall hypothesis that arachidonic acid metabolism contributes to cerebrovascular perturbations induced by perivascular cerebral blood in the newborn brain. Specifically, it is proposed that this contribution involves disruptive activated oxygen species generated initially and during clot lysis that: 1) interfere with production of vasodilatory intermediates and/or prostanoids and 2) promote, either directly or indirectly through tissue damage, production of leukotrienes. To test this hypothesis, three specific aims will be addressed using newborn pigs: 1) determination of the relationship between cerebral production of activated oxygen species and cerebral vascular alterations secondary to perivascular blood; 2) definition of the functional significance of the relationship between production of activated oxygen species caused by perivascular blood and cerebral vascular alterations; and 3) investigation of the mechanisms by which perivascular blood alters vascular reactivity. Cerebral superoxide anion generation, prostanoid and leukotriene production, and hemodynamics during seven days after injection of blood onto the cortical surface and into the caudate nucleus-ventricle will be examined. Key methods include : cranial windows to study the cerebral microcirculation, detect superoxide anion generation, and collect cortical periarachnoid fluid for eicosanoid determinations; radioactively labeled microsphere determination of cerebral blood flow distribution; prostanoid and leukotriene measurement by radioimmunoassay; and superoxide anion detection by superoxide dismutase inhibitable nitroblue tetrazolium reduction. This research will provide important new information in an area where few data are available that ultimately may be of considerable clinical importance since neonatal intracranial hemorrhage is common and can produce lifelong mental and/or physical disability.

这些研究旨在解决总体假设 蛛网膜酸代谢有助于脑血管扰动 新生大脑中血管周围的脑血液诱导。 具体而言，建议这种贡献涉及破坏性 最初以及在凝块溶解期间产生的活性氧种类： 1）干扰血管舒张中间体和/或 前列腺素和2）直接或间接通过组织促进 损坏，白细胞生产。 为了检验这一假设，三个 将使用新生猪解决具体目标：1）确定 活性氧种的大脑产生之间的关系 和脑血管改变继发于血管血管血液； 2） 关系之间关系意义的定义 由血管血液血液和 脑血管改变； 3）调查机制 血管周血血会改变血管反应性。 脑超氧化物 阴离子产生，前列腺素和白三烯产生以及血液动力学 在向皮质表面注入血液后的七天内， 将检查进入尾状核 - 腹膜。 关键方法包括 ：研究脑微循环的颅窗，检测 超氧化阴离子的产生，并收集皮质周围液体的液体 类类测定；放射性标记的微球 确定脑血流分布；前列腺素和 通过放射免疫测定的白三烯测量；和超氧化阴离子 通过超氧化物歧化酶可抑制的氮气四唑检测 减少。 这项研究将为一个重要的新信息提供 几乎没有可用的数据最终可能是相当大的区域 由于新生儿颅内出血很常见，并且 可以产生终生的精神和/或身体残疾。