Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

查看全文 作　　者：Li-Jun [1,2]Jiang;Zhen-Xing [2]Xu;Ming-Fu [2]Wu;Gai-Qin [2]Dong;Li-Li [2]Zhang;Jun-Yan [2]Gao;Chen-Xi [1]Feng;Xing [1]Feng

机构地区：[1]Department of Neonatology,Children's Hospital of Soochow University,Suzhou,Jiangsu Province,China;[2]Department of Neonatology,Affiliated Hospital of Yangzhou University,Yangzhou,Jiangsu Province,China

出　　处：《Neural Regeneration Research》索引2020年第15卷第7期,共10页

基　　金：financially supported by the National Natural Science Foundation of China,No.81771625(to XF);the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF);the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF) 摘　　要：Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018. 关键词：AUTOPHAGY hypoxic-ischemic brain damage neonatal hypoxic-ischemic brain damage NEUROINFLAMMATION nuclear factor kappa-B resatorvid TAK-242 Toll-like receptor 4

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Resatorvid protects against hypoxic-ischemic brain damage in neonatal rats

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