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Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation

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Abstract

Objective and design

Microglia stimulated by oxygen glucose deprivation (OGD) were treated with quercetin to investigate the effect on oxidative stress and the inflammatory response and to explore whether toll-like receptor 4 (TLR4) signaling was involved. In addition, the effect of quercetin on the neurological functions of neonatal mice with hypoxic-ischemic brain injury (HIBI) was examined.

Materials and subjects

Mouse BV2 microglial cells and postnatal day 7 neonatal mice were used.

Treatment

A predetermined concentration of quercetin was used in cell experiments. Quercetin was injected i.p. (50 mg/kg) at three time points after HI insult: 0, 24, and 48 h.

Methods

Cell viability assay, Western blotting, qRT-RCR, ELISA, HIBI model construction and behavioral tests.

Results

This study first showed that quercetin protected BV2 cells from OGD-induced damage and reversed the changes in microglial oxidative stress-related molecules. Second, quercetin inhibited OGD-induced expression of inflammatory factors in BV2 cells and suppressed TLR4/MyD88/NF-κB signaling. Finally, quercetin was disclosed to be effective in mitigating cerebral infarct volume and cognitive and motor function deficits in HIBI mice.

Conclusion

These results suggest that the neuroprotective effect of quercetin in HIBI mice is partially due to the inhibition of oxidative stress and TLR4-mediated inflammatory responses in activated microglia.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (NO. 81760203).

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Author notes

  1. Kai Le and Zhiping Song contributed equally to this work as co-first authors.

Authors and Affiliations

  1. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China

    Kai Le, Jun Zhang, Liang Wang, Lu Zhou, Haidi Bi & Zhen Feng

  2. Department of Anesthesia, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China

    Zhiping Song

  3. Department of Neonatology, The Affiliated Children’s Hospital of Nanchang University, No. 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China

    Jie Deng

  4. Department of Otolaryngology, The Affiliated Children’s Hospital of Nanchang University, No. 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China

    Xin Peng

  5. Department of Orthodontics, School of Stomatology, The Key Laboratory of Oral Biomedicine, Affiliated Stomatological Hospital of Nanchang University, No. 49 Fuzhou Road, Nanchang, 330006, Jiangxi Province, China

    Zhengyu Liao

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  1. Kai Le
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Contributions

ZL and ZF participated in the whole design of this study; KL, ZS, JD, and XP conducted the experiments; KL and XP analyzed the data; KL and ZS wrote original draft; JZ, LW, LZ, HB edited and revised the whole manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Zhengyu Liao or Zhen Feng.

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No potential competing interests was declared by the authors.

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Le, K., Song, Z., Deng, J. et al. Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation. Inflamm. Res. 69, 1201–1213 (2020). https://doi.org/10.1007/s00011-020-01402-5

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  • DOI: https://doi.org/10.1007/s00011-020-01402-5

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