PERINATAL HYPOXIC ISCHEMIC BRAIN DAMAGE

本计划提案的总体目标是改善我们的 对缺氧的病理生理机制的认识 人胎儿和新生儿的缺血性损伤及其发生发展 预防或尽量减少永久性脑损伤的有效策略 最终导致精神发育迟滞或发育障碍。我们的 具体目标包括：1)调查潜在的生物化学 缺氧缺血性脑损伤的发生机制 对围产期动物的损害；2)研究围产期动物的变化 导致缺氧缺血的脑血流和新陈代谢 3)研究其药效及作用机制。 预防或减轻严重程度的特定神经保护剂 围产期缺氧缺血性脑损伤；以及4)确定 或不是长时间或反复发作叠加脑缺氧- 脑缺血会导致或加重最终的脑损伤。全 将在新生大鼠和新生大鼠的发育过程中进行实验 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，后两个项目包括行政和 生物统计学核心、神经病理学核心、磁共振波谱与成像 核心。个人研究项目名称为：1)区域大脑 血流和氧化代谢；2)自由基形成；3)能量 代谢；4)低温循环停止；5)癫痫持续状态。 要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、31P磁共振 光谱学、核磁共振成像、光学和电子显微镜。科学 计划项目中代表的学科是儿科神经病学， 围产期、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。 预计从所述研究中得出的结果 这些努力将与预防和治疗直接相关 必要的干预措施，以大幅降低重要性和 智力发育迟滞与发育障碍的严重程度 人类的婴儿和儿童。

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.