Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway

Wang,Hongyu; Wang,Hongwei; Song,Yinsen; Liu,Congyan; Qian,Xinling; Zhang,Dalong; Jiang,Xin; Zhang,Sisen

doi:10.3892/mmr.2022.12623

Overexpression of Foxc1 ameliorates sepsis‑associated encephalopathy by inhibiting microglial migration and neuroinflammation through the IκBα/NF‑κB pathway

Authors:
- Hongyu Wang
- Hongwei Wang
- Yinsen Song
- Congyan Liu
- Xinling Qian
- Dalong Zhang
- Xin Jiang
- Sisen Zhang
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Affiliations: Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China, Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China, Department of Emergency Medicine, People's Hospital of Henan University of Chinese Medicine/Zhengzhou People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Critical Care Medicine, The Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, Henan 450003, P.R. China, Department of Emergency Medicine, People's Hospital of Henan University of Chinese Medicine/Zhengzhou People's Hospital, Zhengzhou, Henan 450003, P.R. China, Department of Critical Care Medicine, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
Published online on: January 31, 2022 https://doi.org/10.3892/mmr.2022.12623
Article Number: 107
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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