title: Dynamic Modulation of Microglia/Macrophage Polarization by miR-124 after Focal Cerebral Ischemia.
abstract: Mononuclear phagocytes respond to ischemic stroke dynamically, undergoing an early anti-inflammatory and protective phenotype followed by the pro-inflammatory and detrimental type. These dual roles of microglia/macrophages suggest the need of subtle adjustment of their polarization state instead of broad suppression. The most abundant brain-specific miRNA, miR-124, promotes neuronal differentiation but can also modulate microglia activation and keeps them in a quiescent state. We addressed whether the intracerebral injection of miR-124 in a mouse model of ischemic stroke before or after the peak phase of the pro-inflammatory polarization modifies the pro-/anti- inflammatory balance. In the sub-acute phase, 48 h after stroke, liposomated miR-124 shifted the predominantly pro-inflammatory polarized microglia/macrophages toward the anti-inflammatory phenotype. The altered immune response improved neurological deficit at day 6 after stroke. When miR-124 was injected 10 days after stroke, the pro-/anti- inflammatory ratio was still significantly reduced although to a lower degree and had no effect on recovery at day 14. This study indicates that miR-124 administration before the peak of the pro-inflammatory process of stroke is most effective in support of increasing the rehabilitation opportunity in the sub-acute phases of stroke. Our findings highlight the important role of immune cells after stroke and the therapeutic relevance of their polarization balance.
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
authors.forename: Somayyeh
authors.initials: S
authors.lastname: Hamzei Taj
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
authors.forename: Widuri
authors.initials: W
authors.lastname: Kho
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Aswendt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.|Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Franziska M
authors.initials: FM
authors.lastname: Collmann
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Green
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.|Percuros BV, Enschede, Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: Adamczak
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Tennstaedt
authors.affiliation: In-vivo-NMR Laboratory, Max Planck Institute for Metabolism Research, Gleuelerstrasse 50, D-50931, Köln, Germany. mathias@sf.mpg.de.|Department of Radiology, Leiden University Medical Center, Leiden, Netherlands. mathias@sf.mpg.de.|Percuros BV, Enschede, Netherlands. mathias@sf.mpg.de.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology*; D007276:Injections, Intraventricular; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage*; D017628:Microglia / Q000502:physiology*
chemical_list: D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse
keywords: Microglia/macrophage polarization; Neuroinflammation; Pro-inflammatory and anti-inflammatory phenotypes; Stroke; miRNA-124