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Updated: Jul 27, 2026
A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation
Published on: June 10, 2020
Circulating plasma exosomal miR-146b-5p regulates microglial-mediated neuroinflammation through the TRAF6/NF-κB
Fuan Zhang1, Chong Han1, Jiao Chen2
1Department of Neurosurgery, Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Zunyi, Guizhou, 563000, China.
Aims:
The effect of miR-146b-5p on microglial polarization and neuroinflammation post-intracerebral hemorrhage (ICH) remains unclear. We investigated the role of circulating plasma exosomal miR-146b-5p in microglial polarization and neuroinflammation following ICH.
Materials And Methods:
Plasma was isolated from peripheral blood collected from ICH patients and healthy individuals. Bioinformatic analysis identified differentially expressed miRNAs and their target genes. The interaction between miR-146b-5p and its target genes was confirmed using a dual-luciferase reporter assay. Using lipopolysaccharide (LPS)-induced microglial inflammation and ICH mouse models, we assessed the role of miR-146b-5p in microglial polarization and neuroinflammation. miR-146b-5p's regulatory influence on the tumor necrosis factor receptor-associated factor 6/nuclear factor kappa B (TRAF6/NF-κB) pathway was confirmed using knockdown and overexpression experiments of TRAF6.
Key Findings:
The plasma exosome levels of miR-146b-5p in ICH were markedly reduced compared to those in healthy controls. miR-146b-5p overexpression facilitated M2 polarization of microglia and decreased TNF-α, interleukin-1β (IL-1β), and IL-6 levels. Conversely, inhibition of miR-146b-5p had the opposite effect. A dual-luciferase assay indicated that TRAF6 was directly targeted by miR-146b-5p. TRAF6 knockdown inhibited NF-κB activation and enhanced M2 polarization. However, TRAF6 overexpression reversed these effects. Rescue experiments demonstrated that TRAF6 knockdown reversed the phenotypic effects of the miR-146b-5p inhibitor.
Significance:
Circulating plasma exosomal miR-146b-5p modulates microglial polarization and neuroinflammation via the TRAF6/NF-κB signaling pathway following ICH, providing neuroprotective benefits. These findings may contribute to the development of innovative therapeutic approaches.
Insights
Reduced miR-146b-5p in plasma exosomes after intracerebral hemorrhage (ICH) impairs microglial polarization. Restoring miR-146b-5p offers neuroprotection by targeting the TRAF6/NF-κB pathway, suggesting new ICH therapies.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Intracerebral hemorrhage (ICH) triggers neuroinflammation involving microglial polarization.
- The role of microRNA-146b-5p (miR-146b-5p) in ICH-induced microglial changes is not fully understood.
Purpose of the Study:
- To investigate the function of circulating plasma exosomal miR-146b-5p in microglial polarization and neuroinflammation following ICH.
- To elucidate the underlying molecular mechanisms involving the TRAF6/NF-κB pathway.
Main Methods:
- Plasma exosomal miR-146b-5p levels were quantified in ICH patients and healthy controls.
- In vitro and in vivo models (LPS-induced microglia, ICH mouse models) were used to assess miR-146b-5p's effects.
- Dual-luciferase reporter assays and TRAF6 manipulation (knockdown/overexpression) were employed to confirm pathway interactions.
Main Results:
- ICH patients exhibited significantly lower plasma exosomal miR-146b-5p levels compared to controls.
- miR-146b-5p overexpression promoted M2 microglial polarization and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-6).
- miR-146b-5p directly targeted TRAF6, and its inhibition led to TRAF6 upregulation, NF-κB activation, and M1 polarization.
Conclusions:
- Circulating exosomal miR-146b-5p plays a crucial role in regulating microglial polarization and neuroinflammation post-ICH.
- The miR-146b-5p/TRAF6/NF-κB axis represents a potential therapeutic target for mitigating neuroinflammation and promoting neuroprotection in ICH.
