PMID- 32003673 OWN - NLM STAT- MEDLINE DCOM- 20210723 LR - 20210723 IS - 1875-5739 (Electronic) IS - 1567-2026 (Linking) VI - 17 IP - 1 DP - 2020 TI - Forkhead Box O1-p21 Mediates Macrophage Polarization in Postoperative Cognitive Dysfunction Induced by Sevoflurane. PG - 79-85 LID - 10.2174/1567202617666200128142728 [doi] AB - PURPOSE: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. METHODS: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor necrosis factor-alpha (TNF-alpha) were measured. The expression of macrophage phenotype was observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of FoxO1 and p21 were analyzed by immunoblotting (Western blot). RESULTS: Compared with the control group, the freezing time in the anesthesia group was lower than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease of cognitive ability. The blood concentrations of CD163 and TNF-alpha increased significantly at 24 h after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1 phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high level of M1 mRNA, and the expression levels of TNF-alpha, monocyte chemotactic protein 1(MCP-1) and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-beta (TGF-beta) and IL-10 were significantly lower than those in the control group (P<0.05). Compared with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly lower than that in the control group with a significant statistical difference (P<0.01). CONCLUSION: This study offers a theoretical basis and insight for further understanding of the prevention and treatment of cognitive dysfunction induced by anesthetic drugs. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Fu, Jun-Bao AU - Fu JB AD - Department of Anesthesiology, Linyi Central Hospital, Linyi, Shandong, China. FAU - Wang, Zhi-Hua AU - Wang ZH AD - Department of Anesthesiology, Linyi Central Hospital, Linyi, Shandong, China. FAU - Ren, Yong-Ying AU - Ren YY AD - Department of Anesthesiology, Linyi Central Hospital, Linyi, Shandong, China. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Neurovasc Res JT - Current neurovascular research JID - 101208439 RN - 0 (Anesthetics, Inhalation) RN - 0 (Cytokines) RN - 0 (Forkhead Box Protein O1) RN - 0 (Foxo1 protein, mouse) RN - 38LVP0K73A (Sevoflurane) SB - IM MH - Anesthetics, Inhalation/*adverse effects MH - Animals MH - Cell Polarity/*physiology MH - Cytokines/metabolism MH - Forkhead Box Protein O1/*metabolism MH - Hippocampus/metabolism MH - Macrophage Activation MH - Macrophages/*metabolism MH - Male MH - Mice MH - Postoperative Cognitive Complications/chemically induced/*metabolism MH - Sevoflurane/*adverse effects OTO - NOTNLM OT - FoxO1 OT - cognitive dysfunction OT - macrophage polarization OT - p21 OT - sevoflurane OT - ventilation volume. EDAT- 2020/02/01 06:00 MHDA- 2021/07/24 06:00 CRDT- 2020/02/01 06:00 PHST- 2019/11/11 00:00 [received] PHST- 2019/11/21 00:00 [revised] PHST- 2019/11/26 00:00 [accepted] PHST- 2020/02/01 06:00 [pubmed] PHST- 2021/07/24 06:00 [medline] PHST- 2020/02/01 06:00 [entrez] AID - CNR-EPUB-103990 [pii] AID - 10.2174/1567202617666200128142728 [doi] PST - ppublish SO - Curr Neurovasc Res. 2020;17(1):79-85. doi: 10.2174/1567202617666200128142728.