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Updated: Oct 14, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Serum small extracellular vesicles promote M1 activation of microglia after cerebral ischemia/reperfusion injury
Xin Zhou1, Shuyuan Li2, Dachong Chao2
1Institute of Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China; The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China.
Abstract:
Microglial M1 activation is detrimental to stroke outcomes. Recent studies have shown that circulating small extracellular vesicles (sEVs) can deliver miRNAs to target cells and regulate recipient cell functions. Herein, we tested the hypothesis that miRNA delivery by serum sEVs after cerebral ischemia/reperfusion (I/R) injury promote microglial M1 activation, demonstrating that serum sEVs from middle cerebral artery occlusion (MCAO) mice promoted proliferation and M1 activation of BV2 microglia. To explore the underlying mechanism of serum sEVs-mediated microglial activation in the early phase of cerebral I/R injury, we examined the effects of ischemic brain injury on the serum sEVs miRNAs profile in a mouse MCAO model using small RNAseq. Of the 1257 detected miRNA replications, the levels of 72 were significantly modulated. Bioinformatics analysis revealed that a panel of miRNAs was closely associated with inflammation, and in vitro experiments demonstrated that serum sEVs from MCAO mice could effectively transfer inflammatory miRNAs to BV2 microglia. Collectively, our data suggested that miRNAs delivered by serum sEVs after cerebral I/R injury promoted microglial M1 activation. The identification of microglial activation regulators in future studies will give rise to more effective treatments for stroke.
Insights
Serum extracellular vesicles (sEVs) from stroke models deliver inflammatory microRNAs (miRNAs), promoting harmful microglial M1 activation. This highlights sEVs as potential therapeutic targets for stroke treatment.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglial M1 activation exacerbates stroke outcomes.
- Small extracellular vesicles (sEVs) are known to transfer microRNAs (miRNAs) between cells.
- The role of serum sEVs in post-stroke microglial activation remains unclear.
Purpose of the Study:
- To investigate if serum sEVs from ischemic stroke models promote microglial M1 activation.
- To explore the miRNA cargo of serum sEVs following cerebral ischemia/reperfusion (I/R) injury.
- To elucidate the mechanism of serum sEVs-mediated microglial activation.
Main Methods:
- Middle cerebral artery occlusion (MCAO) mouse model for cerebral I/R injury.
- Isolation and characterization of serum small extracellular vesicles (sEVs).
- Small RNA sequencing (small RNAseq) to profile serum sEVs miRNAs.
- In vitro experiments using BV2 microglia to assess MCAO-sEVs effects.
- Bioinformatics analysis of miRNA expression data.
Main Results:
- Serum sEVs from MCAO mice promoted BV2 microglia proliferation and M1 activation.
- Small RNAseq identified 72 significantly modulated miRNAs in serum sEVs post-MCAO.
- Bioinformatics analysis linked modulated miRNAs to inflammatory pathways.
- In vitro studies confirmed transfer of inflammatory miRNAs from MCAO-sEVs to BV2 microglia.
Conclusions:
- Serum sEVs carrying specific miRNAs contribute to microglial M1 activation after cerebral I/R injury.
- These findings suggest that miRNAs within serum sEVs are key mediators of early inflammatory responses post-stroke.
- Targeting these miRNA-carrying sEVs may offer novel therapeutic strategies for stroke treatment.
