title: Melatonin protects against blood-brain barrier damage by inhibiting the TLR4/ NF-κB signaling pathway after LPS treatment in neonatal rats.
abstract: Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms. HII animal model was conducted by receiving lipopolysaccharide followed by 90 min hypoxia-ischaemia in postnatal day 2 Sprague-Dawley rat pups. Melatonin was injected intraperitoneally 1 h before lipopolysaccharide injection and then once a day for 1 week to evaluate the long-term effects. In this study, we demonstrated that melatonin administration inhibited the disruption of BBB permeability and improved the white matter recovery in HII model rats. Melatonin significantly attenuated the degradation of junction proteins and the neuroprotective role was related to the inhibition of microglial toll-like receptor 4/ nuclear factor-kappa B signaling pathway both in vivo and in vitro. Taken together, our data demonstrated that therapeutic strategies targeting inflammation might be suitable for the therapy of preserving BBB integrity after HII.
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhouguang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Pan
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Mingchu
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Huai
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Kebin
authors.initials: K
authors.lastname: Xu
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Zhenmao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Zhenlang
authors.initials: Z
authors.lastname: Lin
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000009:adverse effects; D008550:Melatonin / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D010539:Permeability; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D066127:White Matter / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D008550:Melatonin
keywords: TLR4/NF-κB; blood-brain barrier; hypoxic-ischemic and inflammatory; melatonin; white matter injury