Subtle improvement of seizure susceptibility by atorvastatin treatment during epileptogenesis

Background

The process by which a brain insult elicits epilepsy is termed epileptogenesis and it is characterized by numerous molecular and functional alterations. Statins are first-line drugs for hypercholesterolemia and related diseases, and display neuroprotective properties in clinical and experimental studies. Considering the importance in developing therapeutic strategies to prevent or modify epileptogenesis, we aimed the present study to test the hypothesis that atorvastatin modifies seizure susceptibility of mice after status epilepticus (SE).

Methods

Male and female C57BL/6 mice were submitted to the pilocarpine-induced SE and then treated with atorvastatin (10 or 100 mg/kg, once daily by gavage) for 14 days. At days 7 and 14 post SE we evaluated the susceptibility of mice to the convulsant effects of a low dose of PTZ (30 mg/kg). Cell loss in the hilus of dentate gyrus was evaluated by Giemsa staining.

Results

Latencies to myoclonic jerks and to tonic-clonic seizures decreased between baseline (before SE) and days 7 and 14 after SE, confirming the development of seizure susceptibility. Atorvastatin protected against PTZ-induced tonic-clonic seizures in both sexes at day 14 post-SE. Protective effects were similar in both female and male mice, except that a high dose of atorvastatin was required for females (protection at 100 mg/kg versus 10 mg/kg in males). Giemsa staining did not reveal neuroprotective effects of atorvastatin.

Conclusions

Atorvastatin treatment during epileptogenesis had slight beneficial effects on seizure susceptibility. These seem not related to neuroprotection. Further studies are needed to determine the disease-modifying potential of atorvastatin in epilepsy.