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

Molecular Neurobiology
Reza RahimianJasna Kriz

Abstract

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.

References

Apr 9, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·O ButovskyM Schwartz
Oct 5, 2001·Nature Reviews. Neuroscience·S M Allan, N J Rothwell
Mar 8, 2002·The Journal of Biological Chemistry·Isabelle Pelletier, Sachiko Sato
Jul 12, 2002·Glia·Steven L O'DonnellTeresa L Wood
Mar 23, 2004·Current Drug Targets. Cardiovascular & Haematological Disorders·Kazuyuki Nakajima, Shinichi Kohsaka
Oct 2, 2004·Science·Emily A PartridgeJames W Dennis
Jan 13, 2006·Trends in Neurosciences·Michal SchwartzUwe-Karsten Hanisch
Feb 27, 2007·Cytokine & Growth Factor Reviews·Marta A ToscanoGabriel A Rabinovich
Mar 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mélanie Lalancette-HébertJasna Kriz
Oct 24, 2007·Current Opinion in Structural Biology·Gabriel A RabinovichGerardo R Vasta
Oct 30, 2007·Nature Neuroscience·Uwe-Karsten Hanisch, Helmut Kettenmann
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julie NieminenSachiko Sato
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alison C MacKinnonTariq Sethi
Feb 9, 2008·Stroke; a Journal of Cerebral Circulation·Pierre CordeauJasna Kriz
Jun 6, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jens NeumannKlaus G Reymann
Aug 8, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yubin LiDamo Xu
Sep 16, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gina ZieglerGeorge Trendelenburg
Jul 9, 2011·Nature Medicine·Costantino Iadecola, Josef Anrather
Aug 20, 2011·Stroke; a Journal of Cerebral Circulation·Mélanie Lalancette-HébertJasna Kriz
Jul 28, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mélanie Lalancette-HébertJasna Kriz
Aug 10, 2012·Journal of Neuroinflammation·Ivan BohacekJasna Kriz
Dec 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pampa BhaumikSachiko Sato
Jun 22, 2013·Journal of Neuroinflammation·Starlee Lively, Lyanne C Schlichter
Sep 12, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Isabel Pérez-de PuigAnna M Planas
Dec 10, 2013·Nature Neuroscience·Oleg ButovskyHoward L Weiner
Apr 10, 2014·Nature Reviews. Neuroscience·Marco Prinz, Josef Priller
Jun 4, 2014·Journal of Neuroinflammation·Jonathan D CherryM Kerry O'Banion
Feb 3, 2015·Frontiers in Cellular Neuroscience·Corinne BenakisJosef Anrather
Jan 23, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mathieu GravelJasna Kriz
Sep 17, 2016·Journal of Neuropathology and Experimental Neurology·Starlee LivelyLyanne C Schlichter
May 20, 2017·Nature Reviews. Neurology·Xi LanJian Wang
Nov 15, 2017·Drug Discovery Today·Reza RahimianJasna Kriz

❮ Previous
Next ❯

Citations

Apr 19, 2020·Current Opinion in Neurology·Francisca BarakeAlfonso González
May 28, 2020·Biomolecules·Ivan SrejovicGvozden Rosic
Jun 4, 2020·Marine Drugs·Adrian Florian BălașaAlexandru Mihai Grumezescu
Mar 25, 2020·Phytotherapy Research : PTR·Wenqiang ZhangYue Hou
Jan 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhan-Qi CaoPing Leng
Mar 19, 2021·Medicinal Research Reviews·Reza RahimianJasna Kriz

❮ Previous
Next ❯

Methods Mentioned

BETA
Antibody Array
X-ray
electrophoresis
PCR
co-immunoprecipitation
immunoprecipitation

Software Mentioned

ImageJ
GraphPad Prism
GraphPad
Adobe Photoshop
Living Image

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.