Ventilation Model and CNS Injury in Baboons with BPD

描述（由申请人提供）：产前和新生儿护理的进步显著提高了早产儿的存活率，特别是最不成熟的早产儿。然而，随着这些儿童接近学龄，人们认识到，多达50%的儿童面临神经行为挑战。所有这些神经行为缺陷背后的脑损伤的性质尚不完全清楚，但在脑白质中发现了常见的损伤模式，包括出血和被称为脑室周围白质软化（PVL）的囊性梗死。人们也越来越认识到，在皮层、深灰质和海马体中存在原发性或继发性损伤，这可能与随后的智力损伤有关。至关重要的是，我们要深入了解特定的新生儿实践，如呼吸支持，如何改变这些易感婴儿脑损伤的性质和严重程度。在这项研究中，我们建议利用磁共振成像（MR）和组织病理学来研究早产灵长类动物（Papio sp）作为支气管肺发育不良模型的脑损伤性质。我们的假设是，早产的狒狒（Papio sp）将显示出一种脑损伤的模式，在磁共振成像和组织病理学上很明显，类似于早产的人类婴儿。这种损伤模式将随产后治疗的性质而变化，特别是随机通气策略。对于每个特定目标，方法是相同的，并且将在所有科目中使用最先进的MR成像技术和组织病理学研究。先进的磁共振成像技术将包括常规磁共振成像、定量体积三维成像和扩散张量成像，这是由三个世界级的磁共振研究中心（华盛顿大学、墨尔本大学和哈佛医学院）合作完成的。组织病理学将包括免疫组织化学，包括结构分类，细胞特征-神经元和胶质，生长因子和生化发育。虽然组织病理学技术将是确定脑损伤性质和严重程度的基础，但MR研究将允许将该模型与人类婴儿进行直接比较，我们的项目目前正在对人类婴儿进行相同的体内高级MR研究方案。这些研究可能为新生儿呼吸护理与脑损伤风险的关系提供见解，从而指导我们为未成熟的大脑提供最安全的呼吸支持模式。

DESCRIPTION (provided by applicant): Advances in prenatal and neonatal care have significantly improved survival of the prematurely born infant, particularly the most immature. However, as these children approach school age, it is recognized that up to 50% face neurobehavioral challenges. The nature of the cerebral injury that underlies all of these neurobehavioral deficits is not yet fully understood, but common patterns of injury are found in the cerebral white matter including hemorrhage and cystic infarction known as periventricular leukomalacia (PVL). It is also increasingly recognized that there is primary or secondary injury in the cortical and deep gray matter and the hippocampus, which may relate to subsequent intellectual impairments. It is critical that we gain insight into how particular neonatal practices, such as respiratory support, may alter the nature and the severity of cerebral injury in these vulnerable infants. In this study we propose to investigate the nature of cerebral injury in a prematurely born primate model (Papio sp) developed as a model of bronchopulmonary dysplasia, utilizing both magnetic resonance imaging (MR) and histopathology. Our hypothesis is that the prematurely born baboon (Papio sp) will display a pattern of cerebral injury, evident on MR imaging and histopathology, similar to that found in the prematurely born human infant. This pattern of injury will vary in relation to the nature of postnatal therapies, particularly randomized ventilatory strategies. For each of the specific aims the methodologies are identical and will utilize both state-of-the-art advanced MR imaging techniques and histopathological studies in all subjects. The advanced MR imaging techniques will include conventional MR imaging, quantitative volumetric 3-dimensional imaging and diffusion tensor imaging with collaborations between three-world class research MR sites (Washington University, Melbourne University and Harvard Medical School). The histopathology will include immuno-histochemistry including structural classification, cellular characteristics - neuronal and glial, and growth factor and biochemical development. Although histopathological techniques will be the cornerstone of defining the nature and severity of the cerebral injury, the MR studies will allow a direct comparison between this model and the human infant in whom identical protocols of advanced MR studies in vivo are being currently undertaken in our program. These studies may provide insight into the relationship of neonatal respiratory care to risk of cerebral injury, and thus direct us to the safest modes of ventilatory support for the immature brain.