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Macrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

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Abstract

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain–heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain–heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage–NLRP3 inflammasome activation is a pathway underlying the brain–heart interaction after diabetic stroke.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81771232 and 81974192) and the Natural Science Foundation of Guangdong Province, China (2019A1515010654).

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Author notes

  1. Hong-Bin Lin and Guan-Shan Wei have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China

    Hong-Bin Lin, Guan-Shan Wei, Feng-Xian Li, Wen-Jing Guo, Pu Hong, Ya-Qian Weng, Qian-Qian Zhang, Shi-Yuan Xu & Hong-Fei Zhang

  2. Department of Anesthesiology, Shenzhen SAMII Medical Center, Shenzhen, 518118, China

    Hong-Bin Lin & Zhi-Jian You

  3. Department of Anesthesiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, China

    Hong-Bin Lin

  4. University of Ottawa Heart Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, K1N, Canada

    Wen-Bin Liang

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Lin, HB., Wei, GS., Li, FX. et al. Macrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes. Neurosci. Bull. 36, 1035–1045 (2020). https://doi.org/10.1007/s12264-020-00544-0

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  • DOI: https://doi.org/10.1007/s12264-020-00544-0

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