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

基本信息

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
项目类别：
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

项目摘要

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婴儿的存活率，尤其是最不成熟的婴儿。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挑战。所有这些神经行为缺陷背后的脑损伤的本质尚未完全清楚，但在脑白质中发现了常见的损伤模式，包括出血和囊性梗塞，称为脑室周围白质软化症 (PVL)。人们也越来越认识到，皮质、深层灰质和海马体存在原发性或继发性损伤，这可能与随后的智力障碍有关。至关重要的是，我们必须深入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脑损伤的性质和严重程度。在这项研究中，我们打算利用磁共振成像（MR）和组织病理学来研究早产灵长类动物模型（Papio sp）的脑损伤性质，该模型被开发为支气管肺发育不良模型。我们的假设是，早产狒狒（Papio sp）会表现出一种脑损伤模式，这在磁共振成像和组织病理学上很明显，与早产人类婴儿中发现的情况类似。这种损伤模式会因产后治疗的性质而异，特别是随机通气策略。对于每个具体目标，方法都是相同的，并且将在所有受试者中利用最先进的先进 MR 成像技术和组织病理学研究。先进的 MR 成像技术将包括传统 MR 成像、定量体积 3 维成像和扩散张量成像，以及三个世界级研究 MR 站点（华盛顿大学、墨尔本大学和哈佛医学院）之间的合作。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。尽管组织病理学技术将成为定义脑损伤的性质和严重程度的基石，但 MR 研究将允许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。这些研究可以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通气支持模式。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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.