This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.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.
Specific aim #1 : Characterize the ontogeny of cerebral development in the prematurely born baboon Specific aim #2: Characterize the nature and severity of cerebral injury in the prematurely born baboon.
Specific aim #3 : Evaluate the Influence of three highly clinically relevent therapies aimed at reducing bronchopulomonary dysplasia (BPD) on the pattern of cerebral injury including nitric oxide, antioxidant therapies and anti-inflammatory agents aimed at ductal closure.
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