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MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia

Paper ID Volume ID Publish Year Pages File Format Full-Text
5441 385 2016 15 PDF Available
Title
MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia
Abstract

microRNA-124 (miR-124), the most abundant miRNA of the CNS, was recently shown to modulate the polarization of activated microglia and infiltrating macrophages towards the anti-inflammatory M2 phenotype and protect neurons in various ways after brain disease. In ischemic stroke, microglia and macrophages of a detrimental and persistent pro-inflammatory M1 phenotype have been shown to aggravate the secondary injury. Thus, shifting the polarization of microglia/macrophages into the beneficial, anti-inflammatory M2-like phenotype is considered neuroprotective after stroke onset. Here, we have induced 30 min transient occlusion of the right middle cerebral artery (MCAO) in 34 male, C57BL/6 mice. Lesion development was monitored with T2-weighted MRI. Liposomated miR-124 was injected in 11 animals at 48 h and in 5 animals at 10 days after MCAO. Arg-1, a marker for M2 phenotype, was co-stained with Iba-1, NeuN or GFAP. The distribution of astrocytes, neurons and microglia/macrophages and their expression of Arg-1 were quantified. Early miR-124 injection resulted in a significantly increased neuronal survival and a significantly increased number of M2-like polarized microglia/macrophages. Moreover, the lesion core, delineated by reactive astrocytes, was significantly reduced over time upon early miR-124 injection. These neuroprotective and anti-inflammatory effects of the early miR-124 treatment were pronounced during the first week with Arg-1. Number of Arg-1+ microglia/macrophages correlated with neuronal protection and with functional improvement during the first week. Thus, our present results demonstrate that miR-124 may serve as a novel therapeutic strategy for neuroprotection and functional recovery upon stroke onset.

Keywords
microRNA-124; Ischemic stroke; Immune cell modulation/polarization; Neuroprotection; Functional improvement; Arginase-1
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MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 91, June 2016, Pages 151–165
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us