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NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury.
In: Journal of Neuroinflammation, Jg. 17 (2020-07-23), Heft 1, S. 1-21
Online
academicJournal
Zugriff:
Background: Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation is believed to play a pivotal role, but the underlying mechanism remains unclear. Pyroptosis is a pro-inflammatory form of programmed cell death that triggers inflammatory response upon infection or other stimuli. This study aims to understand the role of microglial pyroptosis in post-cardiac arrest brain injury. Methods: Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Flow cytometry analysis, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), co-immunoprecipitation, and immunofluorescence were used to evaluate activated microglia and CD11b-positive leukocytes after cardiac arrest and assess inflammasome activation and pyroptosis of specific cellular populations. To further explore the underlying mechanism, MCC950 or Ac-YVAD-cmk was administered to block nod-like receptor family protein 3 (NLRP3) or caspase-1, respectively. Results: Our results showed that, in a rat model, successful resuscitation from cardiac arrest resulted in microglial pyroptosis and consequential inflammatory infiltration which was mediated by the activation of NLRP3 inflammasome. Targeting NLRP3 and caspase-1, the executor of pyroptosis, with selective inhibitors MCC950 and Ac-YVAD-cmk treatment significantly prevented microglial pyroptosis, reduced infiltration of leukocytes, improved neurologic outcome, and alleviated neuro-pathological damages after cardiac arrest in modeling rats. Conclusions: This study demonstrates that microglial pyroptosis mediated by NLRP3 inflammasome is critically involved in the pathogenesis of post-cardiac arrest brain injury and provides a new therapeutic strategy. [ABSTRACT FROM AUTHOR]
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NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury.
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Autor/in / Beteiligte Person: | Chang, Yuan ; Zhu, Juan ; Wang, Di ; Li, Hua ; He, Yihua ; Liu, Kewei ; Wang, Xiaoqiang ; Peng, Yuqin ; Pan, Suyue ; Huang, Kaibin |
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Zeitschrift: | Journal of Neuroinflammation, Jg. 17 (2020-07-23), Heft 1, S. 1-21 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 1742-2094 (print) |
DOI: | 10.1186/s12974-020-01879-1 |
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