Open AccessMacrophage–NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes
Author(s) -
Hong-Bin Lin,
Guanshan Wei,
Fengxian Li,
Wenjing Guo,
Hong Peng,
Yaqian Weng,
Qianqian Zhang,
Shiyuan Xu,
Wenbin Liang,
You Zhang,
Hongfei Zhang
Publication year - 2020
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-020-00544-0
Subject(s) - inflammasome , medicine , stroke (engine) , inflammation , diabetes mellitus , pyrin domain , neurology , cardiology , cardiac function curve , systemic inflammation , heart failure , endocrinology , mechanical engineering , psychiatry , engineering
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.