Delayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective

Mol Neurobiol. 2019 Sep;56(9):6371-6385. doi: 10.1007/s12035-019-1527-0. Epub 2019 Feb 23.


Galectin-3 (Gal-3), a β-galactoside-binding lectin, has recently emerged as a molecule with immunoregulatory functions. We investigated the effects of Gal-3 on microglia morphology, migration, and secretory profile under physiological conditions and in the context of ischemic injury. We show that in the control conditions, exposure to recombinant Gal-3 increases microglial ramification and motility in vitro and in vivo via an IL-4-dependent mechanism. Importantly, after stroke, Gal-3 exerted marked immune-modulatory properties. Delivery of Gal-3 at 24 h after middle cerebral artery occlusion (MCAO) was associated with an increase in Ym1-positive microglia and decrease in iNOS. Analysis of cytokine profiles at the protein level revealed downregulation of pro-inflammatory cytokines and a marked upregulation of the anti-inflammatory cytokine, IL-4, 24 h after i.c.v. injection of Gal-3. Importantly, the observed shift in cytokines in microglia was associated with a significant decrease in the infarct size. Taken together, our results suggest that when delivered well after ischemic injury, Gal-3 might fine tune innate immunity and induce a therapeutic shift in microglia polarization.

Keywords: Galectin-3; Innate immunity; Interleukin 4; Microglia; Stroke.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Cell Movement
  • Cell Proliferation
  • Cell Shape
  • Cellular Reprogramming*
  • Cytokines / metabolism
  • Galectin 3 / metabolism*
  • Glucosamine
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Insulin-Like Growth Factor I / metabolism
  • Ligands
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / metabolism*
  • Neuroprotection*
  • Phenotype
  • Stroke / metabolism*
  • Stroke / pathology*
  • Toll-Like Receptor 2 / metabolism


  • Biomarkers
  • Cytokines
  • Galectin 3
  • Ligands
  • Toll-Like Receptor 2
  • Insulin-Like Growth Factor I
  • Glucosamine