Neuroprotective effects of lovastatin in the pilocarpine rat model of epilepsy according to the expression of neurotrophic factors.

Abstract

Studies have suggested that neurotrophic factors (NTFs) are involved in the status epilepticus development. This indicates their essential role in mediating acquired epileptic conditions. Therefore, modulating the expression of NTFs may inhibit seizure-induced cell loss in the epileptic lesions. In this study, we examined the anti-apoptotic, anti-necrotic and regulatory effects of lovastatin on the expression of NTFs in the pilocarpine rat model of temporal lobe epilepsy (TLE). A total of 32 male Wistar rats were divided into 4 groups (n = 8 per group): i) normal; ii) non-treated epileptic group [intraperitoneal (i.p.) administration of 350-400mg/kg pilocarpine]; iii) treatment group (pilocarpine-treated rats treated followed by 5mg/kg lovastatin); and iv) vehicle epileptic rats treated with Carboxymethyl cellulose (CMC). Animals that had a behavioral score of 4-5 according to the Racine scale were selected for study participation. Three days after the first seizure, pilocarpine-treated rats received i.p. injections of lovastatin for 14days. The rats were killed and prepared for histopathologic analysis as well as real-time RT-PCR 17days after the first seizure. The results of this study showed increased mRNA expression of glial cell line-derived neurotrophic factor (GDNF) and Ciliary neurotrophic factor (CNTF) and decreased expressions of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), and Neurotrophin-4 (NT-4) mRNA in the epileptic rats treated with lovastatin. Histological analysis of neurodegeneration in the brain sections showed that the number of hippocampal apoptotic and necrotic cells significantly decreased in the treatment groups. Furthermore, numerical density of neurons per area was significantly higher in the treated groups compared with the untreated groups. Collectively, the results of this study have shown that lovastatin could attenuate seizure-induced expression of neurotrophic factors and consequently reduce hippocampal cell death in the pilocarpine rat model of TLE.