In the neonate, hypoglycemia and hypoxia-ischemia remain the most important causes of brain injury. To develop an effective method to prevent the resultant brain injury, knowledge of the biochemical and physiological derangements unique to the individual disorders is essential. Hypoglycemia in human neonates often occurs together with hypoxia (hypoxic hypoglycemia) or hypotension (hypotensive hypoglycemia). Previous studies have investigated the biochemical derangements that occur during hypoxic or hypotensive hypoglycemia. In contrast, no study thus far has focused on the regulation and alteration of neonatal cerebral blood flow (CBF) during hypoxic or hypotensive hypoglycemia. The piglet hypoglycemia model that we developed offers an excellent in vivo model to study the regulation of CBF during neonatal hypoglycemia. Our hypotheses and research aims are to determine if changes in interstitial fluid concentrations of adenosine during hypoxic and hypotensive hypoglycemia are causally related to changes in blood flow in the neonatal brain, and to elucidate the role of adenosine in postischemic/hypoglycemic hyperemia and hypoperfusion. Our novel modified brain dialysis technique permits simultaneous measurements of interstitial fluid adenosine concentrations and local CBF in the same area of the brain during hypoglycemia. Computerized image analyses of pial arterioles permit examination of temporal changes of pial arterioles in response to administration of adenosine antagonists and agonists during hypoglycemia. CBF measurements with the (14)C- iodoantipyrine autoradiography permit studies of regional CBF during hypoglycemia. Thus, utilization of these three powerful techniques will allow us to thoroughly examine the participation of adenosine in the regulation of CBF during hypoxic and hypotensive hypoglycemia and during postischemic/hypoglycemic reperfusion in the neonate.
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