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  4. Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats

Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats

Journal of Neuroinflammation, 2019 · DOI: https://doi.org/10.1186/s12974-019-1613-2 · Published: October 9, 2019

Spinal Cord InjuryImmunologyNeurology

Simple Explanation

Following a spinal cord injury (SCI), oligodendrocytes (OLs) can die, leading to demyelination and permanent neurological issues. This study investigates whether quercetin, known for its anti-inflammatory properties, can prevent OLs from dying and reduce the immune response mediated by M1 macrophages/microglia after SCI. The study demonstrated that quercetin treatment improved functional recovery in rats after SCI. It was found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Also, myelin loss and axon loss were significantly reduced in quercetin-treated rats, as compared to SCI + saline control. The study also revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. This suggests that targeting necroptosis of OLs could be a potential therapeutic strategy for clinical SCI.

Study Duration
10 and 21 days post injury
Participants
120 male Sprague-Dawley rats
Evidence Level
Not specified

Key Findings

  • 1
    Quercetin treatment improved functional recovery in rats after SCI, as evidenced by significantly higher BBB scores and elevated rump height compared to the control group.
  • 2
    Quercetin significantly reduced necroptosis of OLs after SCI without affecting apoptosis or regeneration. This was confirmed through double staining of RIP3/CC1, MLKL/CC1, and pMLKL/CC1, which showed a reduction in double-positive cells after quercetin treatment.
  • 3
    Quercetin suppressed macrophages/microglia polarization to the M1 phenotype while promoting M2 polarization. This was demonstrated by decreased mRNA levels of M1 markers (TNFα, iNOS, CD86) and increased mRNA levels of M2 markers (Arginase1, IL-4, CD206).

Research Summary

This study investigates the potential of quercetin, an anti-inflammatory agent, to inhibit necroptosis of oligodendrocytes (OLs) and suppress the M1 macrophages/microglia-mediated immune response after spinal cord injury (SCI) in rats. The findings demonstrate that quercetin treatment improved functional recovery in rats after SCI, significantly reduced necroptosis of OLs without affecting apoptosis or regeneration, and attenuated myelin and axon loss. The study reveals that quercetin suppresses macrophages/microglia polarization to M1 phenotype through inhibition of STAT1 and NF-κB pathway, contributing to decreased necroptosis of OLs, suggesting necroptosis of OLs as a potential therapeutic target for clinical SCI.

Practical Implications

Therapeutic Target Identification

Necroptosis of OLs may be a potential therapeutic target for clinical SCI.

Drug Development

Quercetin or similar compounds could be explored for drug development to treat spinal cord injuries.

Clinical Application

Quercetin could be considered as a supplementary treatment to promote functional recovery after SCI.

Study Limitations

  • 1
    The study did not distinguish between microglia and recruited macrophages.
  • 2
    Specific mechanisms for inhibition of M1 polarization by quercetin requires further study.
  • 3
    The study focused on a specific animal model (rats) and may not fully translate to human SCI.

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