Ventilation Model and CNS Injury in Baboons with Bronchopulmonary Dysplasia

支气管肺发育不良狒狒通气模型与中枢神经系统损伤

• 批准号: 7246480
• 负责人: TERRIE E INDER
• 金额: $ 46.08万
• 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 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7246480
• 关键词: 3-Dimensional; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Arts; Astrocytes; Autopsy; Axon; Biochemical; Black-Gold; Brain; Bronchopulmonary Dysplasia; Caring; Cerebral Infarction; Cerebrum; Characteristics; Child; Class; Classification; Cleaved cell; Closure; Collaborations; Control Animal; Data; Depth; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Ductal; Ductus Arteriosus; Environment; Environmental air flow; Evaluation; Face; Foundations; Gestational Age; Glial Fibrillary Acidic Protein; Glial Growth Factor; Glutamates; Growth; Hematoxylin and Eosin Staining Method; Hemorrhage; Hippocampus (Brain); Histocytochemistry; Histology; Histopathology; Human; Hypercapnia; Hypotension; Hypoxia; Image; Imaging Techniques; Impairment; Infant; Infarction; Injury; Intermittent Positive-Pressure Ventilation; International; Knowledge; Lectin; Ligation; Low Birth Weight Infant; Magnetic Resonance; Magnetic Resonance Imaging; Methodology; Microglia; Modeling; Monitor; Myelin; N-Methylaspartate; Nature; Necrosis; Neonatal; Neonatal Intensive Care; Neonatal Intensive Care Units; Neurobiology; Neuroglia; Neurologic; Neurons; Neurotransmitters; Newborn Infant; Nitric Oxide; Outcome; Papio; Pattern; Perinatal Care; Periventricular Leukomalacia; Population; Premature Birth; Premature Infant; Primates; Protocols documentation; Randomized; Relative (related person); Research; Research Design; Research Personnel; Resolution; Respiratory Therapy; Risk; School-Age Population; Scientist; Severities; Site; Staining method; Stains; Standards of Weights and Measures; Structure; Superoxide Dismutase; Survival Rate; Techniques; Texas; Time; United States; Universities; Variant; Washington; Week; analog; base; caspase-3; caspase-7; cell injury; cell type; central nervous system injury; clinically relevant; comparative; cresyl violet; day; gray matter; immunoreactivity; improved; in vivo; insight; medical schools; neonatal human; neurobehavioral; nonhuman primate; postnatal; prenatal; programs; receptor; respiratory; white matter

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步显着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，人们认识到高达50%的儿童面临神经行为方面的挑战。作为所有这些神经行为缺陷的基础的脑损伤的性质尚未完全了解，但在脑白色物质中发现了常见的损伤模式，包括出血和称为脑室周围白质软化（PVL）的囊性梗死。人们也越来越多地认识到，在皮层和深层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障碍有关。关键是，我们要深入了解新生儿的特殊做法，如呼吸支持，可能会改变这些脆弱的婴儿脑损伤的性质和严重程度。在这项研究中，我们建议调查的性质，脑损伤的早产灵长类动物模型（Papio SP）开发的支气管肺发育不良的模型，利用磁共振成像（MR）和组织病理学。我们的假设是，早产的狒狒（Papio sp）将显示一种脑损伤模式，在MR成像和组织病理学上很明显，与早产的人类婴儿相似。这种损伤模式将根据产后治疗的性质而变化，特别是随机治疗策略。对于每个特定目标，方法是相同的，并将在所有受试者中使用最先进的先进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MR成像、定量体积三维成像和扩散张量成像，并与三个世界级研究MR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、生长因子和生化发育。尽管组织病理学技术将是定义脑损伤性质和严重程度的基石，但MR研究将允许在该模型与人类婴儿之间进行直接比较，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。这些研究可能会提供洞察新生儿呼吸道护理的关系，脑损伤的风险，从而指导我们到最安全的模式，为未成熟的大脑的辅助支持。

项目成果

The biological basis of injury and neuroprotection in the fetal and neonatal brain.

• DOI: 10.1016/j.ijdevneu.2011.04.004
• 发表时间: 2011-10
• 期刊: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
• 影响因子: 1.8
• 作者: Rees, Sandra;Harding, Richard;Walker, David
• 通讯作者: Walker, David

MR imaging correlates of white-matter pathology in a preterm baboon model.

磁共振成像与早产狒狒模型中的白质病理学相关。

• DOI: 10.1038/pr.2011.33
• 发表时间: 2012-02
• 期刊: PEDIATRIC RESEARCH
• 影响因子: 3.6
• 作者: Griffith, Jennifer L.;Shimony, Joshua S.;Cousins, Stephanie A.;Rees, Sandra E.;McCurnin, Donald C.;Inder, Terrie E.;Neil, Jeffrey J.
• 通讯作者: Neil, Jeffrey J.