Cortical expression of IL1-β, Bcl-2, Caspase-3 and 9, SEMA-3a, NT-3 and P-glycoprotein as biological markers of intrinsic severity in drug-resistant temporal lobe epilepsy

Abstract

Mesial temporal lobe epilepsy (mTLE) is the most common epilepsy induced by previous cerebral injury, and one out of three mTLE patients develops drug resistance (DR). AimTo assess the expression of Bcl-2, Caspase-3, Caspase-9, IL1-β, SEMA-3a, NT-3 and P-glycoprotein in the temporal cortex and their relationship with the progression of mTLE-DR clinical features in patients with mTLE-DR. MethodTissue samples from 17 patients were evaluated for protein expression by Western blot and the relationships of the evaluated proteins with the clinical features of the mTLE were assessed through hierarchical cluster analysis. ResultsThe mTLE-DR group showed significantly higher P-glycoprotein, Bcl-2 and Caspase-9 levels ***p < 0.0001, ****p < 0.0001 and ***p < 0.0002, respectively, than the autopsy control group. Four patient clusters were identified: Clusters 1 and 3 showed relationships among the age of mTLE onset, duration of mTLE-DR, average number of epileptic seizures per week, number of previous antiepileptic drugs (AEDs) and increased expression of Caspase-3, Caspase-9, Neurotrophin-3 and Semaphorin-3a. Clusters 2 and 4 showed relationships among the mTLE onset age, current age, average number of epileptic seizures per week, number of previous AEDs and increased expression of IL1-β, Bcl-2, P-glycoprotein, Caspase-3 and NT-3. ConclusionThe relationships among the clinical data the age of mTLE onset, DR duration, number of previous AEDs, and average number of seizures per week and the expression of proteins involved in neuronal death, neuroinflammation and aberrant connection formation, as which are biological markers in the cerebral temporal cortex, are important factors in the progression and severity of mTLE-DR and support the intrinsic severity hypothesis.