Funding for this two year project commenced on Oct 1, 1994. One possible mechanism of neonatal resistance to ischemic brain damage is that a highly efficient system of acid regulation to ischemic brain damage gives newborns greater tolerance to injury as compared to adults. Thus newborns may suffer less damage because the total duration of exposure to brain acidosis is shorter than in adults.
The specific aim of the project is to investigate age-related changes in the mechanism of acid regulation following ischemia using in vivo MRS and microdialysis. Changes in cerebral phosphorylated energy metabolites, lactate, and pH were measured during and following ischemia using interleaved 31P and 1H MRS using the 4.7T magnet system. This project is nearing completion with most of the raw data already collected but substantial data analysis still required before publication. In brief, four experiments have been carried out: 1) Fifty swine have been studied to compare the time course of changes in lactate and pH clearance following ischemia in newborn versus 1-month-olds. 2) Thirty swine have been studied to evaluate the effect of cerebral lactic-acidosis on the neurological and histological outcome following ischemia in newborn and 1-month-olds. 3) Fifteen swine have been studied to evaluate the effect of post-ischemic dichloroacetic acid administration on cerebral lactic acid clearance in newborn and 1-month-olds. 4) Fifteen swine have been studied to evaluate the effect of post-ischemic probenecid administration on cerebral lactic acid clearance in newborn and 1-month-olds. Future studies will focus on the use of dichloroacetic acid to reduce brain damage following ischemia, and the use of high resolution 1H MRS and microdialysis to follow the metabolism of 13C labeled glucose following ischemia. Finally, expertise in the simultaneous use of MRS and microdialysis technology developed during the course of this project has also been applied in a preliminary investigation of the effects of exogenous magnesium administration on cerebral intracellular and extracellular fluid magnesium concentrations. It is anticipated that these studies will be extended to evaluate the use of magnesium as a neuroprotective agent following ischemia.
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