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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 (H(2)S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mech...

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Autores principales: Liu, Zhongrui, Zhu, Ziting, He, Yan, Kang, Qiyun, Li, Fei, Zhang, Wenlong, He, Yuehua, Lin, Yuwan, Huang, Baoyi, Mo, Mingshu, Xu, Pingyi, Zhu, Xiaoqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674866/
https://www.ncbi.nlm.nih.gov/pubmed/34924959
http://dx.doi.org/10.3389/fncel.2021.780447
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author Liu, Zhongrui
Zhu, Ziting
He, Yan
Kang, Qiyun
Li, Fei
Zhang, Wenlong
He, Yuehua
Lin, Yuwan
Huang, Baoyi
Mo, Mingshu
Xu, Pingyi
Zhu, Xiaoqin
author_facet Liu, Zhongrui
Zhu, Ziting
He, Yan
Kang, Qiyun
Li, Fei
Zhang, Wenlong
He, Yuehua
Lin, Yuwan
Huang, Baoyi
Mo, Mingshu
Xu, Pingyi
Zhu, Xiaoqin
author_sort Liu, Zhongrui
collection PubMed
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 (H(2)S) 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 H(2)S 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 H(2)S 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 H(2)S 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 H(2)S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H(2)S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H(2)S donor anti-seizures.
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spelling pubmed-86748662021-12-17 A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile Liu, Zhongrui Zhu, Ziting He, Yan Kang, Qiyun Li, Fei Zhang, Wenlong He, Yuehua Lin, Yuwan Huang, Baoyi Mo, Mingshu Xu, Pingyi Zhu, Xiaoqin Front Cell Neurosci Cellular Neuroscience 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 (H(2)S) 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 H(2)S 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 H(2)S 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 H(2)S 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 H(2)S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H(2)S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H(2)S donor anti-seizures. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8674866/ /pubmed/34924959 http://dx.doi.org/10.3389/fncel.2021.780447 Text en Copyright © 2021 Liu, Zhu, He, Kang, Li, Zhang, He, Lin, Huang, Mo, Xu and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Liu, Zhongrui
Zhu, Ziting
He, Yan
Kang, Qiyun
Li, Fei
Zhang, Wenlong
He, Yuehua
Lin, Yuwan
Huang, Baoyi
Mo, Mingshu
Xu, Pingyi
Zhu, Xiaoqin
A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile
title 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_short 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
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674866/
https://www.ncbi.nlm.nih.gov/pubmed/34924959
http://dx.doi.org/10.3389/fncel.2021.780447
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