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5387230 
Journal Article 
Sevoflurane Exerts an Anti-depressive Action by Blocking the HMGB1/TLR4 Pathway in Unpredictable Chronic Mild Stress Rats 
Guo, Z; Zhao, F; Wang, Y; Wang, Y; Geng, M; Zhang, Y; Ma, Q; Xu, X 
2019 
Yes 
Journal of Molecular Neuroscience
ISSN: 0895-8696
EISSN: 1559-1166 
HUMANA PRESS INC 
TOTOWA 
69 
4 
546-556 
English 
31368063 
WOS:000496661000005 
This study was performed to investigate whether sevoflurane has an anti-depressive effect and to elucidate its underlying mechanism. Unpredictable chronic mild stress (uCMS)-treated rats were used for inducing depressive-like behavior and subsequently treated with sevoflurane. A forced swimming test was conducted with the rats. An ELISA was performed to detect the levels of brain-derived neurotrophic factor (BDNF) and inflammatory cytokines in the hippocampus of the rats. Differentially expressed genes in uCMS and normal rats were analyzed by microarray. qRT-PCR, western blot, and flow cytometry, and gain and loss of function measurements were carried out to determine the association between sevoflurane and the HMGB1/TLR4 pathway. A forced swimming test with uCMS rats exposed to sevoflurane demonstrated that a 2% sevoflurane treatment resulted in an anti-depressive effect. In addition, ELISAs of TNF-α (tumor necrosis factor-α), IL-1β (interleukin-1 beta), IL-6 (interleukin-6), and BDNF supported an effect of sevoflurane on inflammatory cytokines and a neurotrophic factor. HMGB1 was dramatically induced in uCMS rats, and the HMGB1/TLR4 pathway was implicated in sevoflurane exposure. A 2% sevoflurane treatment resulted in a restoration of HMGB1/TLR4 signaling and expression of cytokines and BDNF. HMGB1 overexpression partially prevented the protective effect of 2% SF, suggesting sevoflurane protects uCMS rats.