2. Academic Validation
  3. Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes

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

  • Neurosci Bull. 2020 Sep;36(9):1035-1045. doi: 10.1007/s12264-020-00544-0.
Hong-Bin Lin 1 2 3,  Guan-Shan Wei 1,  Feng-Xian Li 1,  Wen-Jing Guo 1,  Pu Hong 1,  Ya-Qian Weng 1,  Qian-Qian Zhang 1,  Shi-Yuan Xu 1,  Wen-Bin Liang 4,  Zhi-Jian You 2,  Hong-Fei Zhang 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China.
  • 2 Department of Anesthesiology, Shenzhen SAMII Medical Center, Shenzhen, 518118, China.
  • 3 Department of Anesthesiology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, 515041, China.
  • 4 University of Ottawa Heart Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ontario, K1N, Canada.
  • 5 Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangzhou, 510220, China. [email protected].
PMID: 32683554 DOI: 10.1007/s12264-020-00544-0
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.

Keywords

Cardiac dysfunction; Diabetes mellitus; Ischemic stroke; Macrophage; NLRP3 inflammasome.

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