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. Epub 2020 Jul 18.

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.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2* / complications
  • Heart Diseases* / etiology
  • Inflammasomes*
  • Ischemic Stroke* / complications
  • Macrophages*
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein*

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse