Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography

Dynamic changes in the regional cerebral glucose metabolic rate induced by hypoxia/reoxygenation or ischemia/reperfusion were investigated with a posi tron autoradiography technique. Fresh rat brain slices were incubated with [F-18]2- fluoro-2-deoxy-D-glucose ([F-18]FDG) in oxygenated Krebs-Ringer so lution at 36 degrees C, and serial two-dimensional time-resolved images of [F-18]FDG uptake in the slices were obtained. In the case of loading hypoxi a (oxygen deprivation)/pseudoischemia (oxygen and glucose deprivation) fur various periods of time, the net influx constant (K) of [F-18]FDG at preloa ding and after reoxygenation/pseudoreperfusion post-loading was quantitativ ely evaluated by applying the Patlak graphical method to the image data. Re gardless of the brain region, with hypoxia lasting greater than or equal to 20 minutes, the postloading K value was decreased compared with the unload ed control, whereas with pseudoischemia of less than or equal to 40 minutes , approximately the same level as the unloaded control was maintained. Next , the neuroprotective effect against hypoxia/pseudoischemia loading induced by the addition of a free radical scavenger or an N-methyl-D-aspartate (NM DA antagonist was assessed by determining whether a decrease in the postloa ding K value was prevented. Whereas with 20-minute hypoxia, both agents exh ibited a neuroprotective effect, in the case of 50-minute pseudoischemia, o nly the NMDA antagonist did so, with the free radical scavenger being ineff ective. These results demonstrate that hypoxia causes irreversible neuronal damage within a shorter period than ischemia, with both free radicals and glutamate suggested to be involved in tandem in the neurotoxicity induced b y hypoxia, whereas glutamate alone is involved in ischemic neurotoxicity.