TROLOX AND 6,7-DINITROQUINOXALINE-2,3-DIONE PREVENT NECROSIS BUT NOT APOPTOSIS IN CULTURED NEURONS SUBJECTED TO OXYGEN DEPRIVATION

There is a growing body of evidence suggesting that apoptosis is invol ved in ischemic brain injury. Recent studies suggest that a rapid necr osis masked a more subtle apoptotic death in neurons subjected to oxyg en deprivation in culture. To test this hypothesis, we treated culture d neurons with potential antinecrotic drugs during and after oxygen de privation. The results show that 6,7-dinitroquinoxaline-2,3-dione (DNQ X) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) , which interfered with kainate receptor activation and lipid peroxida tion respectively, prevented necrosis but allowed neurons to undergo a poptosis. Flow cytometric analysis of DNA degradation and hydrogen per oxide generation, as well as fluorescent microscopy of nuclear fragmen tation revealed that apoptotic activity was higher in DNXQ-treated cel ls than in Trolox-treated cells. This difference in occurrence of apop tosis may be due to the difference in oxidative stress generated from these two different agents. (C) 1998 Elsevier Science B.V.