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 antiseizure 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 (KATP) expression to reduce seizures. The novel H2S donor significantly reduced the expression of TNF-alpha 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 KATP channels blocker. The H2S donor promoted the expression of KATP 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 KATP channels, which may provide a prospective therapeutic strategy for the anti-seizure effects of H2S donor.