Effects of brain IKKß gene silencing by small interfering RNA on P-glycoprotein expression and brain damage in the rat kainic acid-induced seizure model.

Multidrug resistance mediated by over-expression of P-glycoprotein (P-gp) in brain is an important mechanism accounting for the drug-therapy failure in epilepsy. Over-expression of P-gp in epilepsy rat brain may be regulated by inflammation and nuclear factor-kappa B (NF-κB) activation. Inhibitory κ B kinase subunit ß (IKKß) is an up-stream molecular controlling NF-κB activation. With the small interfering RNA (siRNA) technique and kainic acid (KA)-induced rat epileptic seizure model, the present study was aimed to further evaluate the role of NF-κB inhibition, via blocking IKKß gene transcription, in the epileptic brain P-gp over-expression, seizure susceptibility, and post-seizure brain damage. siRNA targeting IKKß was administered to rats via intracerebroventricular injection before seizure induction by KA microinjection; scrambled siRNA was used as control. Brain mRNA and protein levels of IKKß and P-gp were detected by RT-PCR and immunohistochemistry. NF-κB activity was measured by electrophoretic mobility shift assay. Latency to grade III or V seizure onset was recorded, brain damage was evaluated by neuronal cell counting and epileptiform activity was monitored by electroencephalography. IKKß siRNA pre-treatment inhibited NF-κB activation and abolished P-gp over-expression in KA-induced epileptic rat brain, accompanied by decreased seizure susceptibility. These findings suggested that epileptogenic-induced P-gp over-expression could be regulated by IKKß through the NF-κB pathway.

A meta-analysis of pro-inflammatory cytokines in the plasma of epileptic patients with recent seizure.

This review was to assess the concentration changing trends of various cytokines in plasma of epilepsy patients after recent seizure, as well as to assess the differences between temporal lobe epilepsy (TLE) and extra-TLE (XLE) patients. We performed a meta-analysis of studies measuring cytokine concentration in plasma of patients suffering from epilepsy after recent seizure, by searches of the English literature in Pubmed and Embase databases (to July 1st 2010) and a manual search of references. A random-effects model was used to do accumulative analysis for the included studies by RevMan 5.0 software. Eight studies were included and analyzed. We found the plasma concentrations of interleukin-6 (IL-6) within 72h after seizure were significantly increased in epileptic patients compared with control subjects (211 epilepsy patients vs. 564 controls, overall weighted mean difference 1.27pg/ml, 95% confidence interval 0.72-1.82, P<0.0001). There were no significant differences for IL-1 beta and, IL-1 receptor antagonist (IL-1RA) between the two groups. The concentration changes of IL-6 and IL-1RA were not significantly different between TLE patients and XLE patients. The result of this meta-analysis revealed significantly higher concentrations of the pro-inflammatory cytokines IL-6 in epileptic seizure patients compared with control subjects. Further rigorous studies are needed to clarify the precise role of cytokines in epilepsy.