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，特别是最不成熟的婴儿。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，包括出血和囊性脑梗塞，称为脑室周围白质软化症(PVL)。人们也越来越认识到，在皮质和深部灰质以及海马体中存在初级或继发性损伤，这可能与随后的智力损害有关。至关重要的是，我们必须深入了解特定的新生儿做法，如呼吸支持，如何改变这些脆弱婴儿的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模型(Papio Sp)作为支气管肺发育不良模型的脑损伤的性质。我们的假设是，早产的狒狒(Papio Sp)将表现出脑损伤的模式，这在磁共振成像和组织病理学上很明显，类似于在早产的人类婴儿中发现的模式。这种损伤模式将根据出生后治疗的性质而有所不同，特别是随机的呼吸机策略。对于每个特定的目标，方法是相同的，并将利用最先进的先进磁共振成像技术和所有对象的组织病理学研究。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，并与三个世界级的研究磁共振站点(华盛顿大学、墨尔本大学和哈佛医学院)合作。组织病理学将包括免疫组织化学，包括结构分类，细胞特征-神经元和神经胶质，以及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的性质和严重程度的基石，但MR研究将允许在该模型和人类婴儿之间进行直接比较，在我们的项目中，目前正在进行相同的高级体内MR研究方案。这些研究可能会深入了解新生儿呼吸护理与脑损伤风险的关系，从而指导我们为未成熟的大脑提供最安全的呼吸机支持模式。

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.