Efficacy of Ferulic Acid in an Animal Model of Drug-Resistant Epilepsy: Beneficial or Not?

Abstract

Background Lamotrigine (LTG) and subconvulsive doses of pentylenetetrazol (PTZ) as a model mimic drug-resistantepilepsy (DRE), which is a serious unmet medical condition. Previous evidencesuggests an imperative role of neuroinflammation in the development of DRE. Various preclinicalmodels of brain injuryhavereported potent anti-inflammatory and antioxidant properties of ferulic acid (FA). Therefore, its efficacy against intractable epilepsyis worthwhile to study. Materialsand methods The present study evaluated the efficacy of FA in LTG and PTZ-induced refractory seizures in mice. On every alternate day for 38 days, LTG (5mg/kg) was injected before PTZ (30-40mg/kg) to establish a murine model of DRE.Animals were treated with two doses of FA (40, 80mg/kg). All the animals were assessed for seizure score and the latency of seizures every alternate day till the end of the study.Histopathological score and the levels of pro-inflammatory mediators, interleukin-1βeta (IL-Iβ), tumor necrosis factor-alpha (TNF-α),andmatrix metalloproteinase-9 (MMP-9)were quantified in the brain tissue of these mice. Results Ferulic acid (FA) neither decreases the LTG and PTZ-induced refractory seizures score norincreases the latency to developseizures. In addition, theinjury to hippocampal neurons and the levels of pro-inflammatory cytokines were comparable with two doses of FA in treated mice. Conclusion In the present study,single-dose FAtreatment does not show any beneficialeffectagainst the LTG/PTZmodel of DRE. Therefore,its single-dose administration might not be beneficial against the DRE model.