Premium
microRNA‐9‐5p alleviates blood–brain barrier damage and neuroinflammation after traumatic brain injury
Author(s) -
Wu Jingchuan,
He Junchi,
Tian Xiaocui,
Luo Yuetao,
Zhong Jianjun,
Zhang Hongrong,
Li Hui,
Cen Bo,
Jiang Tao,
Sun Xiaochuan
Publication year - 2020
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14963
Subject(s) - neuroinflammation , blood–brain barrier , traumatic brain injury , microrna , apoptosis , pharmacology , hedgehog signaling pathway , in vitro , brain damage , central nervous system , biology , microbiology and biotechnology , medicine , neuroscience , signal transduction , inflammation , immunology , biochemistry , psychiatry , gene
The level of microRNA‐9‐5p (miRNA‐9‐5p) in brain tissues is significantly changed after traumatic brain injury (TBI). However, the effect of miRNA‐9‐5p for brain function in TBI has not been elucidated. In this study, a controlled cortical impact model was used to induce TBI in Sprague–Dawley rats, and an oxygen glucose deprivation model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) and astrocytes were extracted from immature Sprague–Dawley rats and cocultured to reconstruct blood–brain barrier (BBB) in vitro. The results show that the level of miRNA‐9‐5p was significantly increased in brain tissues after TBI, and up‐regulation of miRNA9‐5p contributed to the recovery of neurological function. Up‐regulation of miRNA‐9‐5p with miRNA agomir may significantly alleviate apoptosis, neuroinflammation, and BBB damage in rats after TBI. Moreover, a dual luciferase reporter assay confirmed that miRNA‐9‐5p is a post‐transcriptional modulator of Ptch‐1. In in vitro experiments, the results confirmed that up‐regulation of miRNA‐9‐5p with miRNA mimic alleviates cellular apoptosis, inflammatory response, and BBB damage mainly by inhibiting Ptch‐1. In addition, we found that the activation of Hedgehog pathway was accompanied by inhibition of NF‐κB/MMP‐9 pathway in the BMECs treated with miRNA‐9‐5p mimic. Taken together, these results indicate that up‐regulation of miRNA‐9‐5p alleviates BBB damage and neuroinflammatory responses by activating the Hedgehog pathway and inhibiting NF‐κB/MMP‐9 pathway, which promotes the recovery of neurological function after TBI.