A novel hydrogen sulfide donor reduces neuroinflammation and seizures by activating ATP-sensitive potassium channels

Epilepsy is a common neurological disorder worldwide. Hydrogen sulfide (H₂S) has been found to have anti-seizure effects. However, its mechanism remains to be explored. In the present study, we showed that a novel H₂S donor attenuated neuroinflammation by up-regulating ATP-sensitive potassium channel (K_ATP) expression to reduce seizures. The novel H₂S donor significantly reduced the expression of TNF-α and increased the expression of IL-10 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. The modulatory effects of the H₂S donor on inflammatory cytokines were prevented by glibenclamide, a common K_ATP channels blocker. The H₂S donor promoted the expression of K_ATP channel subunits SUR2 and Kir6.1 in LPS-treated BV2 cells and the hippocampus of pilocarpine-induced epileptic mice. In addition, the H₂S donor reduced the electroencephalography amplitude of hippocampal epileptic waves and reduced seizures in pilocarpine-induced epileptic mice, which were also attenuated by glibenclamide. These results indicated that the novel H₂S donor reduced seizures and regulated microglial inflammatory cytokines by activating K_ATP channels, which may provide a prospective therapeutic strategy for the anti-seizure effects of H₂S donor.