Anticonvulsant activity of atorvastatin against seizure induced by pentylenetetrazole and maximal electroshock in mice

ABSTRACT

Statins are inhibitors of HMG-CoA reductase and inhibit cellular synthesis of cholesterol and isoprenoids. Studies have previously demonstrated the anti-inflammatory and vasoprotective effects of statins on cultured brain cells [astrocytes and microglia] and endothelial cells. Statins have been recently recognized as anti-inflammatory and neuroprotective drugs. Later, neuroprotective effects of statin were reported in various animal disease models and clinical studies. Atorvastatin also prolonged latency [time to appearance of spike potentials] and diminished the amplitude and frequency of spike potentials, which indicate epileptic discharges. In some studies observed that pre-treatment with atorvastatin efficiently reduced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In this study the protective effects of atorvastatin on seizures induced by Pentylenetetrazolee [PTZ] and maximal electroshock stimulation [MES] were investigated. Intraperitoneal pentylenetetrazole was used to induce seizures in mice.It was found that atorvastatin [ED50 = 5.12 +/- 0.98] has antiseizure effects comparing to control group. Atorvastatin treatment significantly increased the seizure threshold [p<0.01] and decreased the incidence of tonic seizure and death which is induced by intraperitoneal pentylenetetrazole . The effect of atorvastatin on seizure induced by MES in mice was evaluated and the results demonstrated it is not able to produce anticonvulsant activity