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We have investigated whether apoptosis or necrosis can be induced in cerebrocortical neurons in culture by overstimulation of glutamate receptors, with consequent influx of excessive Ca2 and downstream production of NO and O2 We used high and low concentrations of glutamate agonists (such as NMDA), NO donors as 3 morpholinosydnonimide (SIN 1) and S nitrosocysteine (SNOC) or peroxynitrite (OONO We found that exposure of cortical cultures to relatively short durations or low concentrations of NMDA, SNOC, SIN 1, or peroxynitrite induced delayed neuronal cell death characterized by apoptotic features. In contrast, intense exposure to high concentrations of NMDA or peroxynitrite induced relatively rapid necrotic cell death in neurons (Bonfoco et al., 1995). Superoxide dismutase (SOD) and catalase attenuated neuronal cell death, most likely by reducing the formation of peroxynitrite because they were only effective if peroxynitrite had not yet formed.
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