Recent studies have clarified the central role of hyperthermia in the reduction of protein synthesis in brain and other tissues following amphetamine administration. The decrease in brain protein synthesis after hyperthermia is not associated with any significant alterations in brain metabolite levels, with the exception of a reduction in glycogen. Studies in the gerbil model have determined the threshold duration of ischemia giving rise to protein synthesis deficits. Repeated short (5 min) ischemic episodes result in more lasting deficits than a single 5 min interval of ischemia produced under similar conditions. Metabolite changes in the repeated ischemia model are now being characterized. Recent collaborative studies have shown that MPP+, the active metabolite of the neurotoxin, MPTP, results in a striking reduction in phosphocreatine levels in primary cultures of cerebellar granule cell neurons prior to any morphological evidence of cell injury. Further evaluation of metabolite changes in this system are in progress.
