Support is requested to study methods that will reliably enable the clinician to predict neurological outcome after perinatal asphyxia. Indicators of outcome that have been used to date such as umbilical cord pH and Apgar scores have proven unreliable. However, MRI has shown distinctive patterns of damage from perinatal asphyxia in the term infant and these patterns have been closely correlated with adverse neurological outcome. It is the hypothesis of this proposal that cerebral perfusion abnormalities and blood brain barrier breakdown are determinants of poor neurological outcome in the neonate and that the measurement of both parameters and the anatomical damage seen on MRI after birth will correlate with the degree of neurological abnormalities seen later in development. Therefore we will define predictors o outcome after asphyxia in term infants using perfusion contrast MRI at 3 days of life. Since excitatory amino acids have been implicated in the pathogenesis of hypoxia-ischemia in the newborn, in vivo measurements of glutamate release and excess should correlate with the areas of perfusion and blood brain barrier breakdown seen on perfusion contrast MRI. Glutamate will be measured by 1H magnetic resonance spectroscopy in the basal ganglia of asphyxiated newborns and compared to CSF glutamate from these infants. The glutamate levels will be correlated with perfusion and blood brain barrier abnormalities. A cohort of babies will be followed for long term longitudinal studies which should provide an accurate assessment of neurological outcome. This approach should enable investigators to more accurately define and study mechanisms of ischemic damage to the neonatal brain and to develop rational therapies aimed at reducing such damage.
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