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

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

  • Neurosci Res. 2023 Jul 11;S0168-0102(23)00139-6. doi: 10.1016/j.neures.2023.07.004.
Qiyun Kang 1 Ziting Zhu 2 Zhongrui Liu 1 Fei Li 1 Yan He 1 Yaru Yang 1 Shuisheng Lei 3 Zishu Yuan 4 Xiaoqin Zhu 5
Affiliations

Affiliations

  • 1 Department of Physiology, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, 510260, Guangzhou, China.
  • 2 Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, China.
  • 3 Department of Physiology, Key Laboratory of Neuroscience, School of Basic Medical Sciences, Department of Dermatology, The Fifth Afliated Hospital of Guangzhou Medical University, 510700, Guangzhou, China.
  • 4 Department of Applied Psychology, School of Health Management, Guangzhou Medical University, 511436, Guangzhou, China. Electronic address: [email protected].
  • 5 Department of Physiology, School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies, Institute of Neuroscience, The Second Affiliated Hospital of Guangzhou Medical University, 510260, Guangzhou, China. Electronic address: [email protected].
Abstract

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 (KATP) 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 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.

Keywords

ATP-sensitive potassium channel; epilepsy; hydrogen sulfide donor; microglial; neuroinflammation.

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