|Title||Delayed Galectin-3-Mediated Reprogramming of Microglia After Stroke is Protective.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Rahimian, Reza, Starlee Lively, Essam Abdelhamid, Mélanie Lalancette-Hébert, Lyanne Schlichter, Sachiko Sato, and Jasna Kriz|
|Date Published||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.
|Alternate Journal||Mol. Neurobiol.|
|Grant List||G-17-0018372 / / Heart and Stroke Foundation of Canada /|