Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest
Yuan Qin,1,* Gangguo Ma,1,* Xiao Xiao,1,* Yongfei Liu,1 Zhaoyan Zhao,1 Fang Zhao,2 Fei Guo,1 Shuang Wang,1 Xude Sun,1 Changjun Gao1 1Department of Anesthesiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China;...
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Dove Medical Press
2025-07-01
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| Series: | Journal of Inflammation Research |
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| author | Qin Y Ma G Xiao X Liu Y Zhao Z Zhao F Guo F Wang S Sun X Gao C |
| author_facet | Qin Y Ma G Xiao X Liu Y Zhao Z Zhao F Guo F Wang S Sun X Gao C |
| author_sort | Qin Y |
| collection | DOAJ |
| description | Yuan Qin,1,* Gangguo Ma,1,* Xiao Xiao,1,* Yongfei Liu,1 Zhaoyan Zhao,1 Fang Zhao,2 Fei Guo,1 Shuang Wang,1 Xude Sun,1 Changjun Gao1 1Department of Anesthesiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changjun Gao, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710000, People’s Republic of China, Email gaocj74@163.comBackground: Neuroinflammation is a critical element to cardiac arrest (CA)-induced global cerebral ischemia injury. Electroacupuncture (EA) treatment has demonstrated therapeutic potentials in both animal and clinical studies for the cerebral ischemic treatment. Nevertheless, the neuroprotective effect of electroacupuncture at ST36 (EA-ST36) in CA-induced global cerebral ischemia injury and the underlying mechanisms remains unclear.Methods: Using a rat model of Asphyxial Cardiac Arrest, the neuroprotective effects of EA-ST36 were evaluated. Single cell RNA-seq analyses were performed to assess the genetic expression of pyroptosis in different cell types of brain. Cognitive performance was tested through the Morris water maze, while neuronal survival, microglial pyroptosis, and neuroinflammation were analyzed by immunofluorescence, flow cytometry, ELISA, and histopathological staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary microglia was established to confirm the role of α 7nAChR in inhibiting pyroptosis.Results: Single-cell RNA sequencing of rat brain and immunofluorescent co-localization showed that pyroptosis is principally occurred in microglia rather than neurons, astrocytes, oligodendrocytes, or endothelial cells in CA/CPR rats. EA-ST36 treatment significantly improved spatial learning and memory in CA/CPR rats, reduced neuronal loss, and attenuated neuroinflammation. These neuroprotective effects were associated with suppressed microglial pyroptosis and decreased IL-1β and IL-18 levels. Remarkably, these neuroprotective effects were abolished by α 7nAChR inhibitors. In vitro, α 7nAChR activation suppressed OGD/R-induced microglial pyroptosis by inhibiting expression of NLRP3, cleaved caspase-1, and N-GSDMD, and decreased IL-1β and IL-18 levels and alleviated the neurotoxic effects of pyroptotic microglia.Conclusion: Our study revealed that EA-ST36 exerted neuroprotective effects with a potent anti-neuroinflammatory potential by suppressing microglial pyroptosis in a rat CA/CPR model, and these anti-neuroinflammatory properties are α 7nAChR-dependent.Keywords: cardiac arrest, neuroinflammation, electroacupuncture, microglia, pyroptosis, α 7nAChR |
| format | Article |
| id | doaj-art-72deb4592f6c4663afce89f6d2011add |
| institution | DOAJ |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj-art-72deb4592f6c4663afce89f6d2011add2025-08-20T02:43:55ZengDove Medical PressJournal of Inflammation Research1178-70312025-07-01Volume 18Issue 187058718104424Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac ArrestQin Y0Ma G1Xiao X2Liu Y3Zhao Z4Zhao F5Guo F6Wang S7Sun X8Gao C9Department of AnesthesiologyDepartment of AnesthesiologyDepartment of Anesthesiology,Department of AnesthesiologyDepartment of AnesthesiologyDepartment of Infectious DiseasesDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyDepartment of AnesthesiologyYuan Qin,1,* Gangguo Ma,1,* Xiao Xiao,1,* Yongfei Liu,1 Zhaoyan Zhao,1 Fang Zhao,2 Fei Guo,1 Shuang Wang,1 Xude Sun,1 Changjun Gao1 1Department of Anesthesiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changjun Gao, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710000, People’s Republic of China, Email gaocj74@163.comBackground: Neuroinflammation is a critical element to cardiac arrest (CA)-induced global cerebral ischemia injury. Electroacupuncture (EA) treatment has demonstrated therapeutic potentials in both animal and clinical studies for the cerebral ischemic treatment. Nevertheless, the neuroprotective effect of electroacupuncture at ST36 (EA-ST36) in CA-induced global cerebral ischemia injury and the underlying mechanisms remains unclear.Methods: Using a rat model of Asphyxial Cardiac Arrest, the neuroprotective effects of EA-ST36 were evaluated. Single cell RNA-seq analyses were performed to assess the genetic expression of pyroptosis in different cell types of brain. Cognitive performance was tested through the Morris water maze, while neuronal survival, microglial pyroptosis, and neuroinflammation were analyzed by immunofluorescence, flow cytometry, ELISA, and histopathological staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary microglia was established to confirm the role of α 7nAChR in inhibiting pyroptosis.Results: Single-cell RNA sequencing of rat brain and immunofluorescent co-localization showed that pyroptosis is principally occurred in microglia rather than neurons, astrocytes, oligodendrocytes, or endothelial cells in CA/CPR rats. EA-ST36 treatment significantly improved spatial learning and memory in CA/CPR rats, reduced neuronal loss, and attenuated neuroinflammation. These neuroprotective effects were associated with suppressed microglial pyroptosis and decreased IL-1β and IL-18 levels. Remarkably, these neuroprotective effects were abolished by α 7nAChR inhibitors. In vitro, α 7nAChR activation suppressed OGD/R-induced microglial pyroptosis by inhibiting expression of NLRP3, cleaved caspase-1, and N-GSDMD, and decreased IL-1β and IL-18 levels and alleviated the neurotoxic effects of pyroptotic microglia.Conclusion: Our study revealed that EA-ST36 exerted neuroprotective effects with a potent anti-neuroinflammatory potential by suppressing microglial pyroptosis in a rat CA/CPR model, and these anti-neuroinflammatory properties are α 7nAChR-dependent.Keywords: cardiac arrest, neuroinflammation, electroacupuncture, microglia, pyroptosis, α 7nAChRhttps://www.dovepress.com/electroacupuncture-at-st36-treatment-suppresses-the-microglial-pyropto-peer-reviewed-fulltext-article-JIRcardiac arrestneuroinflammationelectroacupuncturemicrogliapyroptosisα7nAChR |
| spellingShingle | Qin Y Ma G Xiao X Liu Y Zhao Z Zhao F Guo F Wang S Sun X Gao C Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest Journal of Inflammation Research cardiac arrest neuroinflammation electroacupuncture microglia pyroptosis α7nAChR |
| title | Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest |
| title_full | Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest |
| title_fullStr | Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest |
| title_full_unstemmed | Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest |
| title_short | Electroacupuncture at ST36 Treatment Suppresses the Microglial Pyroptosis Through Activating α7nAChR in a Rat Model of Asphyxial Cardiac Arrest |
| title_sort | electroacupuncture at st36 treatment suppresses the microglial pyroptosis through activating amp alpha 7nachr in a rat model of asphyxial cardiac arrest |
| topic | cardiac arrest neuroinflammation electroacupuncture microglia pyroptosis α7nAChR |
| url | https://www.dovepress.com/electroacupuncture-at-st36-treatment-suppresses-the-microglial-pyropto-peer-reviewed-fulltext-article-JIR |
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