PERINATAL HYPOXIC ISCHEMIC BRAIN DAMAGE

本计划提案的总体目标是改善我们的 了解导致缺氧的病理生理机制- 缺血性损伤的人类胎儿和新生儿和发展 预防或最大限度减少永久性脑损伤的有效策略， 最终导致智力迟钝或发育障碍。 我们 具体目标包括：1）研究潜在的生物化学 缺氧缺血性脑损伤的发生机制 围产期动物的损伤; 2）研究 脑血流量和代谢，最终导致缺氧缺血 脑损伤; 3）研究的疗效和作用机制， 特异性神经保护剂预防或减轻严重程度 围产期缺氧缺血性脑损伤;和4），以确定是否 或不是长时间或反复发作叠加脑缺氧- 局部缺血导致或加重最终的脑损伤。 所有 实验将在发育中的出生后大鼠和新生儿中进行 狗 计划项目建议书中包括五个基础研究项目 和三个核心项目，后两个包括一个行政和 生物统计学核心、神经病理学核心和MR光谱和成像 核心 本研究的课题名称为：1）区域脑 血流和氧化代谢; 2）自由基形成; 3）能量 代谢; 4）低温停循环;和5）癫痫持续状态。 使用的分析技术包括同位素放射自显影， 荧光分光光度法，高压液相色谱法，~（31）P磁共振 光谱学、磁共振成像、光学和电子显微镜。 科学 在该计划项目中代表的学科是儿科神经病学， 围产期学、神经放射学、神经病理学、神经化学、计算机 科学和生物统计学。 预计从所描述的研究中得出的结果 这些努力将直接关系到预防和治疗 采取必要的干预措施， 发展中国家智力迟钝和发展残疾的严重程度 人类婴儿和儿童。

The overall objective of the present Program Proposal is to improve our understanding of the pathophysiologic mechanism leading to hypoxic- ischemic damage in the human fetus and newborn infant and to develop effective strategies to prevent or minimize permanent brain injury which leads ultimately to mental retardation or developmental disability. Our specific aims include: 1) to investigate underlying biochemical mechanisms responsible for the occurrence of hypoxic-ischemic brain damage in perinatal animals; 2) to study the evolution of alterations in cerebral blood flow and metabolism which culminates in hypoxic-ischemia brain damage; 3) to study the efficacy and mechanisms of action of specific neuro-protective agents in preventing or reducing the severity of perinatal hypoxic-ischemic brain damage; and 4) to ascertain whether or not prolonged or repetitive seizure superimposed on cerebral hypoxia- ischemic causes or accentuates the ultimate brain damage. All experiments will be conducted in developing postnatal rats and newborn dogs. Included in the Program Project Proposal are five basic research projects and three Core projects, the latter two include an Administrative and Biostatistics Core, Neuropathology Core, and MR Spectroscopy and Imaging Core. The individual research project titles are: 1) Regional cerebral blood flow and oxidative metabolism; 2) Free radical formation; 3) Energy metabolism; 4) Hypothermic circulatory arrest; and 5) Status epilepticus. Analytical techniques to be utilized include isotopic autoradiography, spectrofluorometry, high pressure liquid chromatography, 31P MR spectroscopy, MR imaging, light and electron microscopy. Scientific disciplines represented in the Program Project are pediatric neurology, perinatology, neuroradiology, neuropathology, neurochemistry, computer science and biostatistics. It is anticipated that the findings derived from the described research endeavors will have direct relevance to preventive and therapeutic interventions necessary to reduce substantially the significance and severity of mental retardation and development disability in developing human infants and children.