Immunomodulatory effect of kainic acid on HMGB1/TLR4 pathway in a thalamic reticular nucleus slice seizure model in rats

Abstract Objective: To explore the relationship between pro-inflammatory factor high-mobility group box 1 (HMGB1) and glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the development of epilepsy. Methods: Thalamic reticular nucleus (TRN) slice was treated with kainic acid (KA) to simulate seizure. Seizure-like spikes and spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded within TRN slices using whole-cell patch clamp techniques. The translocation of HMGB1 were detected by Immunofluorescence. HMGB1/TLR4 signaling pathway and its downstream inflammatory factors (IL-1β and NF-κB) were detected by RT-PCR, Western blot and ELISA. Results: KA-evoked seizure-like spikes were observed in the TRN slices and blocked by perampanel. sIPSCs in the TRN were enhanced by KA and blocked by perampanel. The translocation of HMGB1 in TRN were promoted by KA and inhibited by perampanel. The expression of HMGB1/TLR4 signaling pathway were promoted by KA and suppressed by perampanel. Conclusion: The AMPA receptor and HMGB1/TLR4 signaling pathway interaction jointly contribute to the development of epilepsy.