Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway.
机构：[1]Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280[2]Department of Emergency Medicine, People's Hospital of Henan University of Chinese Medicine/Zhengzhou People's Hospital[3]Department of Critical Care Medicine, The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan 450003[4]Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China
Sepsis‑associated encephalopathy (SAE) is a common and severe complication of sepsis. The cognitive dysfunction that ensues during SAE has been reported to be caused by impairments of the hippocampus. Microglia serves a key role in neuroinflammation during SAE through migration. Forkhead box C1 (Foxc1) is a member of the forkhead transcription factor family that has been found to regulate in cell migration. However, the role of Foxc1 in neuroinflammation during SAE remains unknown. In the present study, the mechanistic role of Foxc1 on microglial migration, neuroinflammation and neuronal apoptosis during the occurrence of cognitive dysfunction in SAE was investigated. A microglia‑mediated inflammation model was induced by LPS in BV‑2 microglial cells in vitro, whilst a SAE‑related cognitive impairment model was established in mice using cecal ligation and perforation (CLP) surgery. Cognitive function in mice was evaluated using the Morris Water Maze (MWM) trial. Lipopolysaccharide (LPS) treatment was found to trigger BV‑2 cell migration, inflammation and neuronal apoptosis. In addition, CLP surgery induced cognitive injury, which was indicated by longer latencies and shorter dwell times in the goal quadrant compared with those in the Sham group in the MWM trial. LPS treatment or CLP induction decreased the expression of Foxc1 and inhibitor of NF‑κB (IκΒα) whilst increasing that of p65, IL‑1β and TNF‑α. After Foxc1 was overexpressed, the cognitive dysfunction of mice that underwent CLP surgery was improved, with the expression of IκBα also increased, microglial cell migration, the expression of p65, IL‑1β and TNF‑α and neuronal apoptosis were all decreased in vivo and in vitro, which were in turn reversed by the inhibition of IκBα in vitro. Overall, these results suggest that the overexpression of Foxc1 inhibited microglial migration whilst suppressing the inflammatory response and neuronal apoptosis by regulating the IκBα/NF‑κB pathway, thereby improving cognitive dysfunction during SAE.
基金：
Chinese International Medical
Exchange Foundation 2021 (grant no. Z‑2016‑23‑2101‑37),
Cardiovascular Multidisciplinary Integrated Thinking
Research Fund (grant no. z‑2016‑23‑2101‑37) and Key
Scientific Research Project Plan of Henan University (grant
no. 20A320007).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|4 区医学
小类|4 区肿瘤学4 区医学：研究与实验
最新[2025]版：
大类|4 区医学
小类|4 区医学：研究与实验4 区肿瘤学
第一作者：
第一作者机构：[1]Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280[2]Department of Emergency Medicine, People's Hospital of Henan University of Chinese Medicine/Zhengzhou People's Hospital[3]Department of Critical Care Medicine, The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan 450003
通讯作者：
通讯机构：[1]Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280[2]Department of Emergency Medicine, People's Hospital of Henan University of Chinese Medicine/Zhengzhou People's Hospital[3]Department of Critical Care Medicine, The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan 450003[4]Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China[*1]Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, 1023‑1063 Shatai South Road, Baiyun, Guangzhou, Guangdong 510280, P.R. China[*2]Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Yangpu, Shanghai 200092, P.R. China
推荐引用方式(GB/T 7714)：
Wang Hongyu,Wang Hongwei,Song Yinsen,et al.Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway.[J].Molecular medicine reports.2022,25(3):doi:10.3892/mmr.2022.12623.
APA：
Wang Hongyu,Wang Hongwei,Song Yinsen,Liu Congyan,Qian Xinling...&Zhang Sisen.(2022).Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway..Molecular medicine reports,25,(3)
MLA：
Wang Hongyu,et al."Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway.".Molecular medicine reports 25..3(2022)
