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Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor
Cumulative evidence suggests that pyroptosis, a new sort of programmed cell death, is closely related to cerebral ischemia/reperfusion (I/R) injury. Our previous studies have testified that vagus nerve stimulation (VNS) was involved in many different neuroprotective and neuroplasticity pathways via...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825823/ https://www.ncbi.nlm.nih.gov/pubmed/35136042 http://dx.doi.org/10.1038/s41420-022-00852-6 |
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author | Tang, Hao Li, Jiani Zhou, Qinxiang Li, Sheng Xie, Chenchen Niu, Lingchuan Ma, Jingxi Li, Changqing |
author_facet | Tang, Hao Li, Jiani Zhou, Qinxiang Li, Sheng Xie, Chenchen Niu, Lingchuan Ma, Jingxi Li, Changqing |
author_sort | Tang, Hao |
collection | PubMed |
description | Cumulative evidence suggests that pyroptosis, a new sort of programmed cell death, is closely related to cerebral ischemia/reperfusion (I/R) injury. Our previous studies have testified that vagus nerve stimulation (VNS) was involved in many different neuroprotective and neuroplasticity pathways via α7 nicotinic acetylcholine receptor (α7nAchR), a vital node of the cholinergic anti-inflammatory pathway during cerebral I/R injury. We aimed to determine the neuroprotective effects of VNS through α7nAchR-mediated inhibition of pyroptosis. Focal cerebral ischemic stroke rat models were obtained by middle cerebral artery occlusion for 120 min. Expression of the NLRP3 inflammasome was evaluated using western blotting and immunofluorescence (IF) staining. The neurological deficit score, infarct volume, TUNEL staining findings, transmission electron microscopy findings, and expression of inflammatory cytokines were assessed 3 days after I/R injury. Our findings suggested that the protein expression levels of NLRP3, GSDMD-N, cleaved caspase-1, and ASC gradually increased until they peaked on day 3 after I/R injury. VNS inhibited the expression of pyroptosis-related molecules and decreased the number of pyroptotic cells and membrane pores. Administration of α7nAchR-antagonist and agonist helped in further assessment of the role of α7nAchR in pyroptosis. α7nAchR-agonist mimicked VNS’s neuroprotective effects on the improvement of neurological deficits, the reduction of infarct volumes, and the inhibition of neuronal pyroptosis after cerebral I/R injury. Conversely, the neuroprotection provided by VNS could be reversed by the administration of α7nAchR-antagonist. In conclusion, VNS-induced neuroprotection via inhibition of neuronal pyroptosis was α7nAchR-dependent, highlighting the pivotal role of α7nAChR in suppressing cellular pyroptosis and neuroinflammation. These findings may allow a better understanding of treatment principles for cerebral I/R injury. |
format | Online Article Text |
id | pubmed-8825823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88258232022-02-17 Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor Tang, Hao Li, Jiani Zhou, Qinxiang Li, Sheng Xie, Chenchen Niu, Lingchuan Ma, Jingxi Li, Changqing Cell Death Discov Article Cumulative evidence suggests that pyroptosis, a new sort of programmed cell death, is closely related to cerebral ischemia/reperfusion (I/R) injury. Our previous studies have testified that vagus nerve stimulation (VNS) was involved in many different neuroprotective and neuroplasticity pathways via α7 nicotinic acetylcholine receptor (α7nAchR), a vital node of the cholinergic anti-inflammatory pathway during cerebral I/R injury. We aimed to determine the neuroprotective effects of VNS through α7nAchR-mediated inhibition of pyroptosis. Focal cerebral ischemic stroke rat models were obtained by middle cerebral artery occlusion for 120 min. Expression of the NLRP3 inflammasome was evaluated using western blotting and immunofluorescence (IF) staining. The neurological deficit score, infarct volume, TUNEL staining findings, transmission electron microscopy findings, and expression of inflammatory cytokines were assessed 3 days after I/R injury. Our findings suggested that the protein expression levels of NLRP3, GSDMD-N, cleaved caspase-1, and ASC gradually increased until they peaked on day 3 after I/R injury. VNS inhibited the expression of pyroptosis-related molecules and decreased the number of pyroptotic cells and membrane pores. Administration of α7nAchR-antagonist and agonist helped in further assessment of the role of α7nAchR in pyroptosis. α7nAchR-agonist mimicked VNS’s neuroprotective effects on the improvement of neurological deficits, the reduction of infarct volumes, and the inhibition of neuronal pyroptosis after cerebral I/R injury. Conversely, the neuroprotection provided by VNS could be reversed by the administration of α7nAchR-antagonist. In conclusion, VNS-induced neuroprotection via inhibition of neuronal pyroptosis was α7nAchR-dependent, highlighting the pivotal role of α7nAChR in suppressing cellular pyroptosis and neuroinflammation. These findings may allow a better understanding of treatment principles for cerebral I/R injury. Nature Publishing Group UK 2022-02-08 /pmc/articles/PMC8825823/ /pubmed/35136042 http://dx.doi.org/10.1038/s41420-022-00852-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tang, Hao Li, Jiani Zhou, Qinxiang Li, Sheng Xie, Chenchen Niu, Lingchuan Ma, Jingxi Li, Changqing Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title | Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title_full | Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title_fullStr | Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title_full_unstemmed | Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title_short | Vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
title_sort | vagus nerve stimulation alleviated cerebral ischemia and reperfusion injury in rats by inhibiting pyroptosis via α7 nicotinic acetylcholine receptor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8825823/ https://www.ncbi.nlm.nih.gov/pubmed/35136042 http://dx.doi.org/10.1038/s41420-022-00852-6 |
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