Potential anti-seizure activity of atorvastatin in rat models of seizure

Abstract

Background: Atorvastatin belongs to the class of Hypolipidemic statins. Increasing evidence indicates that statins are neuroprotective in several conditions, including stroke, cerebral ischemia and traumatic brain injury. However, only scanty and controversial reports are available on anticonvulsant action of statins. The present study therefore aims at exploring the influence of atorvastatin on seizures as compared to standard anticonvulsants phenytoin and sodium valproate in Wistar rats. Methods: Rats were divided into 8 groups (n=6), each treated intraperitoneally (i.p) with atorvastatin, phenytoin or sodium valproate in their therapeutic equivalent doses. Their effects were evaluated on seizures induced by maximum electroshock seizure (MES) and pentylenetetrazole (PTZ). Hind limb extension (HLE) in MES model, number of seizures, duration of seizure, number of myoclonic jerks and time for onset as well as recovery from seizures in PTZ model were monitored. Statistical analysis was done using Kruskal-Wallis ANOVA and Mann-Whitney U test for significance. Results: Atorvastatin failed to protect rats against HLE in MES seizure model. However, atorvastatin significantly prolonged seizure onset time (p<0.0547), decreased seizure number (p<0.0082), seizure duration (p<0.0547) and recovery time (p<0.0040) in PTZ model indicating its potential antiepileptic activity in PTZ model. Conclusions: Atorvastatin exhibited protection against seizures only in PTZ seizure model. Hence, it could possess anti absence seizure activity. This needs to be established with further systematic animal and clinical studies.