OXIDATIVE MECHANISMS INVOLVED IN KAINATE-INDUCED CYTOTOXICITY IN CORTICAL-NEURONS

In our previous experiments, evidence of free radical formation has be en demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radi cal formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, a-phenyl-N-tert-butyl-nitrone (PBN), as well as the combined action o f superoxide dismutase and catalase attenuated KA neurotoxic effect. C alpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopur inol, a selective XO inhibitor, significantly protected the cortical n eurons from KA-induced cell death. However, XO activation may not be t he only source producing free radicals, other free radical generating systems such as nitric oxide synthase may also play a role in KA insul t.