Dynamic Modulation of Microglia-Macrophage Polarization by miR-124 after Focal Cerebral IschemiaReportar como inadecuado




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Journal of Neuroimmune Pharmacology

, Volume 11, Issue 4, pp 733–748

First Online: 18 August 2016Received: 05 July 2016Accepted: 28 July 2016

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.

KeywordsStroke Microglia-macrophage polarization Pro-inflammatory and anti-inflammatory phenotypes miRNA-124 Neuroinflammation Electronic supplementary materialThe online version of this article doi:10.1007-s11481-016-9700-y contains supplementary material, which is available to authorized users.

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Autor: Somayyeh Hamzei Taj - Widuri Kho - Markus Aswendt - Franziska M. Collmann - Claudia Green - Joanna Adamczak - Annette Tenn

Fuente: https://link.springer.com/







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