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Updated: Oct 11, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
The natural (poly)phenols as modulators of microglia polarization via TLR4/NF-κB pathway exert anti-inflammatory
Ruoqi Li1, Yuan Zhou1, Shanshan Zhang1
1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Abstract:
Increasing evidences suggest that inflammation plays a key role in the pathogenesis of stroke, a devastating disease second only to cardiac ischemia as a cause of death worldwide. Microglia are the first non-neuronal cells on the scene during the innate immune response to acute ischemic stroke. Microglia respond to acute brain injury by activating and developing classic M1-like (pro-inflammatory) or alternative M2-like (anti-inflammatory) phenotypes. M1 microglia produce pro-inflammatory cytokines to exacerbate neural death, astrocyte apoptosis, and blood brain barrier (BBB) disruption, while M2 microglia play the opposite role. NF-κB, a central regulator of the inflammatory response, was responsible for microglia M1 and M2 polarization. NF-κB p65 and p50 form a heterodimer to initiate a pro-inflammatory cytokine response, which enhances M1 activation and impair M2 response of microglia. TLR4, expressed on the surface of microglia, plays an important role in activating NF-κB, ultimately causing the M1 response of microglia. Therefore, modulation of microglial phenotypes via TLR4/NF-κB signaling pathway may be a promising therapeutic approach for ischemic stroke. Dietary (poly)phenols are present in various foods, which have shown promising protective effects on ischemic stroke. In vivo studies strongly suggest that many (poly)phenols have a pronounced impact on ischemic stroke, as demonstrated by lower neuroinflammation. Thus, this review focuses on the anti-inflammatory properties of dietary (poly)phenols and discusses their effects on the polarization of microglia through modulating TLR4/NF-κB signaling pathway in the ischemic stroke.
Insights
Dietary polyphenols reduce neuroinflammation in stroke by modulating microglial polarization. They target the TLR4/NF-κB pathway, shifting microglia from pro-inflammatory M1 to anti-inflammatory M2 phenotypes for stroke recovery.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Inflammation is a key factor in stroke pathogenesis.
- Microglia, the brain's immune cells, adopt M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes post-stroke.
- The Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway regulates microglial polarization.
Purpose of the Study:
- To review the anti-inflammatory effects of dietary polyphenols in ischemic stroke.
- To explore how polyphenols modulate microglial polarization via the TLR4/NF-κB pathway.
- To highlight potential therapeutic strategies for stroke targeting neuroinflammation.
Main Methods:
- Review of in vivo studies on dietary polyphenols and ischemic stroke.
- Analysis of the role of TLR4/NF-κB signaling in microglial activation.
- Focus on polyphenol-induced shifts in M1/M2 microglial phenotypes.
Main Results:
- Dietary polyphenols demonstrate significant neuroprotective effects in ischemic stroke models.
- Polyphenols can reduce neuroinflammation by influencing microglial polarization.
- Modulation of the TLR4/NF-κB pathway is a key mechanism for polyphenol action.
Conclusions:
- Dietary polyphenols hold therapeutic promise for ischemic stroke.
- Targeting microglial polarization through the TLR4/NF-κB pathway is a viable strategy.
- Further research into specific polyphenols could lead to novel stroke treatments.
