Neurochemistry international
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We tested whether rosuvastatin (RST) protected against excitotoxic neuronal cell death in rat primary cortical neuronal cultures. L-glutamate (200 microM, 1h) reduced neuronal viability (% of naive controls, mean+/-SEM, n=8-32, *p<0.05) from 100+/-2% to 60+/-1%*, but pretreatment with RST (0.5 microM, 3 days) increased survival to 88+/-2%*. RST-induced neuroprotection was not affected by co-application with mevalonate (10 microM), although the same dose of mevalonate fully prevented the neurotoxic effects of a high dose (20 microM) of RST. ⋯ In contrast, acute, one time RST application did not affect either baseline or L-glutamate-induced increases in superoxide levels. In summary, three-day RST pretreatment induces resistance to the excitotoxic effect of L-glutamate in cultured neurons apparently by a mechanism that is independent of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition. The delayed neuroprotection by RST against excitotoxicity does not involve sustained mitochondrial depolarization or superoxide anion production as initiating events, although it is associated with reduced Ca(2+) influx and superoxide anion production upon L-glutamate challenge.