A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile

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 mechan...

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Autores principales: Zhongrui Liu, Ziting Zhu, Yan He, Qiyun Kang, Fei Li, Wenlong Zhang, Yuehua He, Yuwan Lin, Baoyi Huang, Mingshu Mo, Pingyi Xu, Xiaoqin Zhu
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:4deb0b1dea884317bb4c24f270ce7f5a2021-12-02T10:26:25ZA Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile1662-510210.3389/fncel.2021.780447https://doaj.org/article/4deb0b1dea884317bb4c24f270ce7f5a2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fncel.2021.780447/fullhttps://doaj.org/toc/1662-5102Although 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.Zhongrui LiuZhongrui LiuZiting ZhuYan HeYan HeQiyun KangQiyun KangFei LiFei LiWenlong ZhangYuehua HeYuehua HeYuwan LinBaoyi HuangBaoyi HuangMingshu MoPingyi XuXiaoqin ZhuXiaoqin ZhuFrontiers Media S.A.articlehydrogen sulfide donorstatus epilepticus (SE)inflammatory profileneuroinflammationpilocarpineNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Cellular Neuroscience, Vol 15 (2021)
institution DOAJ
collection DOAJ
language EN
topic hydrogen sulfide donor
status epilepticus (SE)
inflammatory profile
neuroinflammation
pilocarpine
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle hydrogen sulfide donor
status epilepticus (SE)
inflammatory profile
neuroinflammation
pilocarpine
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Zhongrui Liu
Zhongrui Liu
Ziting Zhu
Yan He
Yan He
Qiyun Kang
Qiyun Kang
Fei Li
Fei Li
Wenlong Zhang
Yuehua He
Yuehua He
Yuwan Lin
Baoyi Huang
Baoyi Huang
Mingshu Mo
Pingyi Xu
Xiaoqin Zhu
Xiaoqin Zhu
A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
description 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.
format article
author Zhongrui Liu
Zhongrui Liu
Ziting Zhu
Yan He
Yan He
Qiyun Kang
Qiyun Kang
Fei Li
Fei Li
Wenlong Zhang
Yuehua He
Yuehua He
Yuwan Lin
Baoyi Huang
Baoyi Huang
Mingshu Mo
Pingyi Xu
Xiaoqin Zhu
Xiaoqin Zhu
author_facet Zhongrui Liu
Zhongrui Liu
Ziting Zhu
Yan He
Yan He
Qiyun Kang
Qiyun Kang
Fei Li
Fei Li
Wenlong Zhang
Yuehua He
Yuehua He
Yuwan Lin
Baoyi Huang
Baoyi Huang
Mingshu Mo
Pingyi Xu
Xiaoqin Zhu
Xiaoqin Zhu
author_sort Zhongrui Liu
title A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title_short A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title_full A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title_fullStr A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title_full_unstemmed A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title_sort novel hydrogen sulfide donor reduces pilocarpine-induced status epilepticus and regulates microglial inflammatory profile
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/4deb0b1dea884317bb4c24f270ce7f5a
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