Ventilation Model and CNS Injury in Baboons with BPD

BPD狒狒的通气模型和中枢神经系统损伤

• 批准号: 7107147
• 负责人: TERRIE E INDER
• 金额: $ 46.67万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7107147
• 关键词: antiinflammatory agents; baboons; bronchopulmonary dysplasia; central nervous system disorders; developmental neurobiology; disease /disorder model; electroencephalography; histopathology; hypercapnia; hypotension; hypoxia; immunocytochemistry; magnetic resonance imaging; neonatal intensive care; neurogenesis; nitric oxide; nonhuman therapy evaluation; positive pressure breathing; premature infant animal; premature infant human; pulmonary respiration; respiratory disorder chemotherapy; respiratory therapy; superoxide dismutase

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.

描述（由申请人提供）：产前和新生儿护理的进展显着改善了早产婴儿的生存，尤其是最未成熟的婴儿。但是，随着这些孩子接近学龄的年龄，人们认识到，多达50％的人面临神经行为的挑战。尚未完全了解所有这些神经行为缺陷的大脑损伤的性质，但是在脑白质中发现了常见的损伤模式，包括出血和囊性梗塞被称为腹膜周围白细胞性白细胞（PVL）。还越来越认识到，皮质和深灰质和海马的一级或继发性损伤可能与随后的智力障碍有关。至关重要的是，我们了解特定的新生儿实践（例如呼吸支持）如何改变这些脆弱婴儿的大脑损伤的性质和严重程度，这一点至关重要。在这项研究中，我们建议在使用磁共振成像（MR）和组织病理学的过早出生的灵长类动物模型（Papio SP）中研究脑损伤的性质（Papio SP）。我们的假设是，过早出生的狒狒（Papio SP）将显示出大脑损伤的模式，这与MR成像和组织病理学相似，类似于在过早出生的人类婴儿中发现的模式。这种损伤模式与产后疗法的性质，尤其是随机通气策略有关。对于每个特定目的，方法都是相同的，并且将在所有受试者中同时利用最先进的先进MR成像技术和组织病理学研究。先进的MR成像技术将包括常规的MR成像，定量体积3维成像和扩散量张量成像，并与三个世界类别研究MR站点（华盛顿大学，墨尔本大学和哈佛医学院）之间的合作进行合作。组织病理学将包括免疫 - 归化学，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。尽管组织病理学技术将是定义大脑损伤性质和严重性的基石，但MR研究将允许该模型与人类婴儿之间的直接比较，在我们的计划中，目前正在进行Vivo先进MR研究的相同方案。这些研究可能会洞悉新生儿呼吸道护理与脑损伤风险的关系，从而将我们引向对未成熟大脑的最安全的通气支持模式。