Core--Animal Assessment

描述(由申请人提供)： 早产会导致学龄儿童严重的认知障碍。MRI研究和配对 对学龄期极低出生体重儿的神经心理测试表明 严重的认知障碍以及相关的形态学改变。我们假设 伴随着早产的慢性亚致死性缺氧干扰了发育。 早产儿大脑的程序性成熟。这种损伤导致了不适当的阶段性 早期和晚期的发育线索，以及相应的长期变化 发育中的大脑中的皮质醇生成。一种临床相关模型的建立 早产需要选择一种忠于胚胎发育阶段的动物模型 被研究的婴儿，损伤研究的文件会导致神经病理变化和 这种损伤与行为结果的相关性。该计划项目的首要目标是， 正如在四个研究项目中所例证的，是理解这一现象的分子基础 复杂的病理学。在核心A中，我们描述了用于生成动物模型的协议， 基于一段时间的新生儿亚致死缺氧期。核心B，动物评估的目标 核心是为我们的动物分析提供一个复杂而统一的基础设施 模型和在每个项目中进行的实验操作的影响。核心B 还将添加独立于项目的附加数据，从而允许更完整的 了解该模型及其与早产的相关性。特定能力 该核心提供的服务包括：i)脑形态的定量测量；ii)系列磁共振成像 评估行为(功能磁共振)、皮质体积(体积成像)和白质 物质发展(扩散张量成像)；三)模型的行为和认知测试 动物；以及iv)选定大脑区域转录事件的微阵列分析。 统计服务也将由核心B提供。核心提供的数据， 连同每个项目直接提供的数据，将由 生物统计工具的综合集合。通过对动物的统一评估，核心B 将协同项目之间的互动，并促进最全面的 可用数据的利用率。

DESCRIPTION (provided by applicant): Preterm birth results in significant cognitive disability at school age. MRI studies and pair neuropsychological testing of very low birth weight infants at school age demonstrate both significant cognitive handicap as well as correlative morphologic changes. We hypothesize that the chronic sublethal hypoxia that accompanies preterm birth disrupts the developmentally programmed maturation of the preterm brain. This injury results in the inappropriate phasing of both early and late developmental cues, with consequential long-term changes in corticogenesis in the developing brain. The development of a clinically relevant model of preterm birth requires selection of an animal model faithful to the developmental stage of the infants studied, documentation that the injury studied produces neuropathologic change and correlation of that injury with behavioral outcome. An overarching goal of this Program Project, as exemplified in the four investigational projects, is to understand the molecular basis of this complex pathology. In Core A, we describe our protocol for generating our animal model, based on a period of sublethal neonatal hypoxia. The goal of Core B, the Animal Assessment Core, is to provide a sophisticated and uniform infrastructure for the analysis of our animal model and the impact of experimental manipulations carried out in each of the projects. Core B will also add additional data independent of the projects that will allow a more complete understanding of the model and its relevance to premature birth. Specific competencies provided by this core include i) quantitative measurements of brain morphology; ii) serial MRI assessments of behavior (functional MRI), cortical volume (volumetric imaging) and white matter development (diffusion tensor imaging); iii) behavioral and cognitive testing of the model animals; and iv) microarray analysis of transcriptional events in selected brain regions. Statistical services will also be provided by provided by Core B. The data provided by the core, together with the data provided directly by each of the Projects, will be analyzed by a comprehensive ensemble of biostatistical tools. By the uniform assessment of animals, Core B will synergize the interactions between projects, and facilitate the most comprehensive utilization of the available data.