The neuroprotective mechanism of sevoflurane in rats with traumatic brain injury via FGF2

Journal of Neuroinflammation

Zhaoyang Wang¹  Fei Xing¹  Juan Li¹  Xin Wei¹  Wei Zhang¹  Zhongyu Wang¹  Na Xing¹  Jingjing Yuan¹  Anqi Wang¹  Junmin Wang² 

[1] Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, 450052, Zhengzhou, Henan Province, People’s Republic of China;Henan Province International Joint Laboratory of Pain, Cognition and Emotion, the First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, 450052, Zhengzhou, Henan Province, People’s Republic of China;Department of Human Anatomy, Basic Medical College of Zhengzhou University, 450001, Zhengzhou, Henan Province, People’s Republic of China;

关键词: Traumatic brain injury;    Sevoflurane;    FGF2;    EZH2;    HES1;    Neuroprotection;    Neuronal apoptosis;    Neurological deficits;   

DOI  :  10.1186/s12974-021-02348-z

来源: Springer

【 摘 要 】

BackgroundTraumatic brain injury (TBI) is a kind of acquired brain injury, which is caused by external mechanical forces. Moreover, the neuroprotective role of sevoflurane (Sevo) has been identified in TBI. Therefore, this research was conducted to figure out the mechanism of Sevo in TBI via FGF2.MethodsThe key factors of neuroprotective effects of Sevo in TBI rats were predicted by bioinformatics analysis. A TBI model was induced on rats that then inhaled Sevo for 1 h and grouped via lentivirus injection. Modified Neurological Severity Score was adopted to evaluate neuronal damage in rats, followed by motor function and brain water content measurement. FGF2, EZH2, and HES1 expression in brain tissues was evaluated by immunofluorescence staining, and expression of related genes and autophagy factors by RT-qPCR and Western blot analysis. Methylation-specific PCR was performed to assess HES1 promoter methylation level, and ChIP assay to detect the enrichment of EZH2 in the HES1 promoter. Neuronal damage was assessed by cell immunofluorescence staining, and neuronal apoptosis by Nissl staining, TUNEL staining, and flow cytometry.ResultsSevo diminished brain edema, improved neurological scores, and decreased neuronal apoptosis and autophagy in TBI rats. Sevo preconditioning could upregulate FGF2 that elevated EZH2 expression, and EZH2 bound to the HES1 promoter to downregulate HES1 in TBI rats. Also, FGF2 or EZH2 overexpression or HES silencing decreased brain edema, neurological deficits, and neuronal autophagy and apoptosis in Sevo-treated TBI rats.ConclusionsOur results provided a novel insight to the neuroprotective mechanism of Sevo in TBI rats by downregulating HES1 via FGF2/EZH2 axis activation.

【 授权许可】

CC BY