Effects of pioglitazone in the thalamus and anterior olfactory nuclei in the rat lithium- pilocarpine model of temporal lobe epilepsy

Background and aims: Thalamus and anterior olfactory nuclei have been previously recognized as areas with the high level of acute neuronal loss in rodent models of temporal lobe epilepsy (TLE). These structures, being parts of the complex neuronal network within the limbic system, participate in the initiation and propagation of seizures and might contribute to the process of epileptogenesis. The purposes of this study were to investigate oxidative lipid damage, inflammation and endogenous neuroprotection in these brain structures during the early genesis of TLE as well as the effects of the PPAR-γ agonist pioglitazone on the examined parameters. Methods: SE was induced by administration of pilocarpine 22 h after lithium chloride and 30 min after methylscopolamine. Rats were injected with pioglitazone (1 ; 3 mg/kg) or vehicle i.p. 10 min after SE onset and sacrificed 24 h thereafter. Levels of the brain lipid peroxidation products were determined by the thiobarbituric acid reactive substances (TBARS) assay. COX-2 and HSP70 expressions were analyzed by Western blotting. Results: At 24 h after SE, TBARS level and HSP70 expression were unchanged and COX-2 was not detectable in the thalamus. In anterior olfactory nuclei, increased level of TBARS as well as enhanced expressions of COX-2 and HSP70 were detected. Treatment with pioglitazone resulted in enhanced HSP70 expression in the thalamus and reduced TBARS level in anterior olfactory nuclei, compared to levels obtained in vehicle-treated rats with SE. Conclusion: Pioglitazone exerts neuroprotective effects in the thalamus and anterior olfactory nuclei in the rat lithium- pilocarpine model of TLE.