Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation
- Inflamm Res. 2020 Dec;69(12):1201-1213. doi: 10.1007/s00011-020-01402-5.
- 1. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
- 2. Department of Anesthesia, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China.
- 3. Department of Neonatology, The Affiliated Children's Hospital of Nanchang University, No. 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China.
- 4. Department of Otolaryngology, The Affiliated Children's Hospital of Nanchang University, No. 122 Yangming Road, Nanchang, 330006, Jiangxi Province, China.
- 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. [email protected].
- 6. Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi Province, China. [email protected].
- # Contributed equally.
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.