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

TitleDelayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective.
Publication TypeJournal Article
Year of Publication2019
AuteursRahimian, R, Lively, S, Abdelhamid, E, Lalancette-Hébert, M, Schlichter, L, Sato, S, Kriz, J
JournalMol Neurobiol
Date Published2019 Sep
KeywordsAnimals, Biomarkers, Brain Ischemia, Cell Movement, Cell Proliferation, Cell Shape, Cellular Reprogramming, Cytokines, Galectin 3, Glucosamine, Infarction, Middle Cerebral Artery, Insulin-Like Growth Factor I, Ligands, Mice, Inbred C57BL, Mice, Transgenic, Microglia, Neuroprotection, Phenotype, Stroke, Toll-Like Receptor 2

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.

Alternate JournalMol. Neurobiol.
PubMed ID30798442
Grant ListG-17-0018372 / / Heart and Stroke Foundation of Canada /