The Abnormal Expression Of IRAK1in Brain Tissue Of Patient With Intractable Temporal Lobe Epilepsy And A Rat Model And The Influence Of IRAK1Inhibition On Rat Ethology In A SE Model

Background: Neuroinflammation occurs after seizures and isimplicated in epileptogenesis. Interleukin-1receptor associated kinase(IRAKs) are key mediators in the signaling pathways of TLRs/IL-1Rs.By means of their kinase and adaptor functions, IRAKs initiate a cascadeof signaling events eventually leading to induction of inflammatory targetgene expression. In IRAKs family, IRAK1and IRAK4exhibit kinaseactivity. In this work IRAK1expression were examined in brain tissue ofthe patients with intractable temporal lobe epilepsy and a rat model oftemporal lobe epilepsy（TLE）at different time points following statusepilepticus (SE) induced by pilocarpine injection. We also studied theinfluence of IRAK1/4inhibitor on SE rats about the frequency andseverity of seizures. Methods: Twenty temporal neocortex tissue samplesfrom patients with intractable temporal lobe epilepsy and six normaltemporal lobe from control were selected. In rat model, SE was inducedby pilocarpine injection. Control rats were injected with saline instead ofpilocarpine. Rats were sacrificed in different time point. Usingimmunohistochemistry, immunofluorescence, and Western blotting, weexamined IRAK1expression in the hippocampus of rats with temporallobe epilepsy. In SE model, IRAK1/4inhibitor was intraperitoneal injected, seizure frequency and severity were observed in model groupand intervention group. Results: IRAK1expression was significantlyhigher in TLE patients as compared with the control. Increased IRAK1was observed in the rat hippocampus after SE. IRAK1positive cells werecolocalization with neurons but not glial cells. In Li-Pilo induced SEmodel, the number of seizures was decreased and the severity of seizurewas alleviated in intervention group. Conclusion: The data show thatIRAK1was up-regulated in TLE patients and the hippocampus of ratafter pilocarpine-induced epilepsy. IRAK1/4inhibitor decrease thenumber of seizures and alleviate the severity of seizure in SE model.These data implicate IRAK1in the pathophysiology of epilepsy. IRAK1might as a therapeutic target for epilepsy.