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Cited by 152Extracellular vesicles in diseaseNeuroinflammation and Neurodegeneration MechanismsNeurogenesis and neuroplasticity mechanisms

M2 microglia-derived extracellular vesicles promote white matter repair and functional recovery via miR-23a-5p after cerebral ischemia in mice

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Li, Yongfang, Liu, Ze, Song, Yaying, Pan, Jia-ji, Jiang, Yixu, Shi, Xiaojing, Liu, Chang, Ma, Yuanyuan +9 more·2022·Theranostics
DOI 10.7150/thno.68895PMC PMC9065182
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Abstract

Rationale: White matter repair is critical for the cognitive and neurological functional recovery after ischemic stroke.M2 microglia are well-documented to enhance remyelination and their extracellular vesicles (EVs) mediate cellular function after brain injury.However, whether M2 microglia-derived EVs could promote white matter repair after cerebral ischemia and its underlying mechanism are largely unknown.Methods: EVs were isolated from IL-4 treated microglia (M2-EVs) and untreated microglia (M0-EVs).Adult ICR mice subjected to 90-minute transient middle cerebral artery occlusion received intravenous EVs treatment for seven consecutive days.Brain atrophy volume, neurobehavioral tests were examined within 28 days following ischemia.Immunohistochemistry, myelin transmission electron microscope and compound action potential measurement were performed to assess white matter structural remodeling, functional repair and oligodendrogenesis.The effects of M2-EVs on oligodendrocyte precursor cells (OPCs) were also examined in vitro.EVs' miRNA sequencing, specific miR-23a-5p knockdown in M2-EVs and luciferase reporter assay were used to explore the underlying mechanism.Results: M2-EVs reduced brain atrophy volume, promoted functional recovery, oligodendrogenesis and white matter repair in vivo, increased OPC proliferation, survival and differentiation in vitro.miR-23a-5p was enriched in M2-EVs and could promote OPC proliferation, survival and maturation, while knocking down miR-23a-5p in M2-EVs reversed the beneficial effects of M2-EVs both in vitro and in vivo.Luciferase reporter assay showed that miR-23a-5p directly targeted Olig3.Conclusion: Our results demonstrated that M2 microglia could communicate to OPCs through M2-EVs and promote white matter repair via miR-23a-5p possibly by directly targeting Olig3 after ischemic stroke, suggesting M2-EVs is a novel and promising therapeutic strategy for white matter repair in stroke and demyelinating disease.

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  • Expression of miR-23a-5p in extracellular vesicles derived from M2 microglia is elevated after cerebral ischemia in mice, and it can advance white matter repair and brain function recovery after ischemic stroke by targeting Olig3.

    “On the other hand, the expression of miR-23a-5p in extracellular vesicles derived from M2 microglia is elevated after cerebral ischemia in mice, and it can advance white matter repair and brain function recovery after ischemic stroke by functioning on target gene Olig3 [66].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [66]

    The Results section (‘MiR-23a-5p was enriched in M2-EVs and enhanced oligodendrogenesis in vitro’; page not provided) reports higher miR-23a-5p in M2-EVs than M0-EVs, not an increase caused by cerebral ischemia. The Discussion (page not provided) supports a role for EV-carried miR-23a-5p in white matter repair and functional recovery after stroke, but describes mediation through Olig3 as possible rather than established. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Li, Y., Liu, Z., Song, Y., Pan, J.-J., Jiang, Y., Shi, X., Liu, C., Ma, Y., Luo, L., Mamtilahun, M., Shi, Z., Khan, H., Xie, Q., Wang, Y., Tang, Y., Zhang, Z., & Yang, G.-Y.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Shanghai Medical College of Fudan University (CN)
Corresponding author
  • Zhang, Zhijun
  • Yang, Guo-Yuan
ORCID
Venue
Theranostics
Publisher
Ivyspring International Publisher
Published
2022
Volume
12
Issue
7
Pages
3553-3573
ISSN
1838-7640 (ISSN-L)
DOI
10.7150/thno.68895
PMC
PMC9065182
OpenAlex
W4285174564
Cited by
152
References
5
Citations by year
2026: 29 · 2025: 52 · 2024: 40 · 2023: 21 · 2022: 10
FWCI
10.04
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Theranostics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (82001228, ZH2018ZDA04, 81801170, 81974179, 81771244, 81771251, 81870921, 2019-01)
  • Shanghai Jiao Tong University (ZH2018ZDA04)
  • K. C. Wong Education Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
M2 microglia, extracellular vesicles, white matter repair, ischemic stroke, miR-23a-5p, oligodendrocyte precursor cells, oligodendrogenesis, functional recovery, remyelination, IL-4, demyelinating disease
MeSH terms
Extracellular Vesicles, Ischemic Stroke, Animals, Atrophy, Brain Ischemia, Mice, Inbred ICR, Microglia, MicroRNAs, Mice, White Matter

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