This is an application to establish an Experimental Neonatal Brain Disorders Center focused on the vulnerability of the developing brain to hypoxia and ischemia. The application is divided into two Preclinical Projects and three Clinical Projects, all supported by three Cores. Taken as a whole, the project will provide valuable diagnostic and therapeutic information relevant to newborn brain injury. Project 1, The Neuropharmacology of Cortical Injury, contains experiments that explore the role of excitatory amino acids in neuronal injury in fetal and newborn rats and in brain slices obtained from focal cortical resections in humans. These should help elucidate the cellular pathophysiology of neuronal injury. Project 2, Intraventricular Hemorrhage and Cerebrovascular Reactivity, will investigate the role of vasospasm and altered vascular reactivity in newborn brain injury associated with intracranial bleeding. This information may suggest alternate therapies for newborns with cerebral hemorrhage. Project 3, Doppler Evaluation of Fetal Neurological Integrity, will determine whether quantitative ultrasound examinations show characteristic patterns in neurologically normal and abnormal fetuses. These examinations may help identify high risk newborns in utero. Project 4, Cerebral Blood Flow and Metabolism in Newborn Infants, will use positron emission tomography to measure glucose metabolism in newborns and also validate near infrared spectroscopy as a noninvasive indicator of cerebral blood flow. These results could alter the fluid and respiratory management of critically ill neonates. Project 5, Nuclear Magnetic Resonance Imaging of Diffusion Coefficient and Blood Flow, will determine whether NMR techniques can noninvasively identify early brain damage in sick newborns and whether they can localize abnormalities of cerebral blood flow. This information could alter management of these infants.
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