Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons |
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Authors: | Yu Cheng Albert Y. Sun |
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Affiliation: | (1) Department of Pharmacology, University of Missouri-Columbia School of Medicine, 65212 Columbia, Missouri |
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Abstract: | In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical 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 of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synphase may also play a role in KA insult. |
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Keywords: | Free radicals kainic acid cortical neuron a-phenyl-N-tert-butyl-nitrone excitotoxicity xanthine oxidase |
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