Rosuvastatin induces delayed preconditioning against L-glutamate excitotoxicity in cultured cortical neurons.

Neurochemistry International
Ferenc DomokiDavid W Busija

Abstract

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. RST (0.5 microM) pretreatment did not affect mitochondrial membrane potential or superoxide anion levels in quiescent neurons. However, RST pretreatment blunted elevations in free intracellular Ca(2+) and reduced increases in superoxide anion levels following glutamate exposure. Manganese superoxide dismutase (SOD), copper-zinc SOD, catalase, and reduced glutathione levels were unaffected by RST pretreatment. 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 inde...Continue Reading

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Mar 31, 2007·Journal of Neurochemistry·Tamás GáspárDavid W Busija
Jun 20, 2007·Neurochemistry International·Alan S Hazell
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Jan 10, 2008·Journal of Neurochemistry·Tamás GáspárDavid W Busija
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Jul 31, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Keita MayanagiDavid W Busija

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Citations

Aug 2, 2014·European Journal of Pharmacology·Ramazan KahveciBülent Erdoğan
Oct 6, 2018·Clinical and Experimental Pharmacology & Physiology·Ibraheem HusainAbul K Najmi
Dec 31, 2010·Current Opinion in Neurology

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