Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-me
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Inflammation Research
ORIGINAL RESEARCH PAPER
Quercetin alleviates neonatal hypoxic‑ischemic brain injury by inhibiting microglia‑derived oxidative stress and TLR4‑mediated inflammation Kai Le1 · Zhiping Song2 · Jie Deng3 · Xin Peng4 · Jun Zhang1 · Liang Wang1 · Lu Zhou1 · Haidi Bi1 · Zhengyu Liao5 · Zhen Feng1 Received: 13 June 2020 / Revised: 10 September 2020 / Accepted: 14 September 2020 © Springer Nature Switzerland AG 2020
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. Keywords Hypoxic-ischemic brain injury · Quercetin · Microglia · TLR4 · Oxidative stress
Introduction
Responsible Editor: John Di Battista. Kai Le and Zhiping Song contributed equally to this work as cofirst authors. * Zhengyu Liao [email protected] * Zhen Feng [email protected] 1
2
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang 330006, Jiangxi Province, China Department of Anesthesia, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang 330006, Jiangxi Province, China
The incidence of neonatal hypoxic-ischemic brain injury (HIBI) caused by insufficient cerebral blood flow or/and oxygen supply is still high, especially in developing countries, which directly leads to approximately 24% of neonatal deaths worldwide every year and results in long-term, 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, J
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