NEWBORN CEREBRAL HEMORRHAGE AND ARACHIDONATE METABOLITES

新生儿脑出血和花生四烯酸代谢物

• 批准号: 3361174
• 负责人: CHARLES W. LEFFLER
• 金额: $ 16.9万
• 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/3361174
• 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.

这些研究旨在解决以下总体假设： 花生四烯酸代谢导致脑血管紊乱 由新生儿大脑血管周围脑血引起。 具体来说，建议这项贡献涉及破坏性 最初和在凝块溶解过程中产生的活性氧： 1) 干扰血管舒张中间体的产生和/或 前列腺素和 2) 直接或间接通过组织促进 损伤，白三烯的产生。 为了检验这个假设，三个 将使用新生猪来实现具体目标：1) 确定 大脑产生活性氧之间的关系 继发于血管周围血液的脑血管改变； 2） 定义之间关系的功能意义 血管周围血液引起的活性氧的产生和 脑血管改变； 3）研究机制 血管周围的血液改变血管反应性。 脑超氧化物 阴离子的产生、类前列腺素和白三烯的产生以及血流动力学 将血液注射到皮质表面后 7 天内， 将检查尾状核心室。 关键方法包括 ：颅窗研究脑微循环，检测 产生超氧阴离子，并收集皮质蛛网膜周围液 类二十烷酸测定；放射性标记微球 测定脑血流分布；前列腺素和 通过放射免疫测定法测量白三烯；和超氧阴离子 超氧化物歧化酶抑制硝基四唑蓝检测 减少。 这项研究将提供重要的新信息 可用数据很少但最终可能具有相当大的数据的领域 由于新生儿颅内出血很常见，因此临床意义重大 可能造成终生精神和/或身体残疾。