Abstract
Although epilepsy is one of the most common neurologic disorders, there is still a lack of effective therapeutic drugs for it. Recently, we synthesized a novel hydrogen sulfide (H2S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mechanism. In the present study, we found that the novel H2S donor could reduce pilocarpine-induced seizures in mice. It alleviated the epileptic behavior, the hippocampal electroencephalography (EEG) activity of seizures, and the damage of hippocampal neurons in status epilepticus mice. In addition, the novel H2S donor could reduce microglial inflammatory response. It not only reduced the upregulation of pro-inflammatory markers [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)] in status epilepticus mice, but also increased the levels of microglial anti-inflammatory marker arginase-1 (Arg-1). In lipopolysaccharide-treated microglia BV2 cells, administration of the H2S donor also significantly reduced the lipopolysaccharide-induced upregulation of the expression of the pro-inflammatory markers and increased the expression of the anti-inflammatory markers. Thus, the novel H2S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H2S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H2S donor anti-seizures.
Highlights
Epilepsy, a nervous system disorder characterized by sudden abnormal hypersynchrony of neurons, affects 70 million people in the world
The H2S donor decreased the amplitudes of epileptic wave in status epilepticus (SE) mice (ANOVA, p < 0.001) (Figure 1D).These results suggested that the H2S donor reduced seizures in pilocarpineinduced mice model
The present study indicated that the novel H2S donor reduced seizures in pilocarpine-induced mice model
Summary
A nervous system disorder characterized by sudden abnormal hypersynchrony of neurons, affects 70 million people in the world. While under the stimulation of specific drugs or cytokines (such as resveratrol or IL-4), the expression of several proteins including arginase-1 (Arg1) and the production of anti-inflammatory cytokines such as IL-10, IL-4, and IL13 increased in microglia (Gordon, 2003; Benson et al, 2015; Yang et al, 2017; Therajaran et al, 2020; Zhang et al, 2021). The “activated” microglia have exhibited heterogeneity in their phenotypes, which makes it difficult to determine whether these microglia are proepileptic or antiepileptic (Hiragi et al, 2018) Both microglial pro-inflammatory cytokines (IL1β and TNF-α) and anti-inflammatory cytokines (IL-4 and IL-10) showed increased expression after pilocarpine-induced status epilepticus, indicating a complex role of microglia in the epileptic brain (Hu et al, 2015). Modulation of microglial inflammatory profile will become a potential therapeutic strategy for epilepsy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
