The overall objective of this project is to elucidate biochemical and physiologic mechanisms responsible for perinatal hypoxic-ischemic brain damage and to develop strategies which will arrest or retard these processes.
Specific aims i nclude: 1) to characterize those critical cellular metabolic events which precede or parallel the evolution of include: 1) to characterize those critical cellular metabolic events which precede or parallel the evolution of identifiable lesions resulting from cerebral hypoxia-ischemia in the immature rat; 2) to investigate the apparent identifiable lesions resulting from cerebral hypoxia-ischemia in the immature rat; 2) to investigate the apparent delayed or secondary energy failure which occurs during recovery from hypoxia-ischemia in the immature rat and to determine whether or not the phenomenon causes or contributes to brain damage; 3) to investigate further the beneficial effect of carbon dioxide on hypoxic-ischemic brain damage in the developing rat; and 4) to investigate further the influence of alterations in glucose and lactate homeostasis on hypoxic-ischemic brain damage in the developing rat and to identify those mechanisms whereby glucose exerts a beneficial or harmful effect on neuropathologic outcome. To accomplish these goals, the Principal Investigator will use the following analytical techniques: 1) the iodo-{14C}-antipyrine technique to measure cerebral blood flow; 2) the 2-deoxy-[14C]-glucose and [4C]-glucose techniques to measure cerebral glucose utilization; 3) in vivo analysis of glycolytic and Krebs cycle intermediates and high-energy phosphates reserves in brain tissues; 4) determination of cerebral energy utilization, intracellular pH, and the redox state of brain tissue; 5) regional analysis of calcium and sodium uptake and turnover by brain; 6) histopathologic analysis of brain specimens; and 7) MR spectroscopy.
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