Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice
Copyright © 2022 Elsevier B.V. All rights reserved..
With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has anti-neuroinflammation effects by modulating microglial polarization and inhibiting astrocyte activation. In this study, we demonstrated that the inhalation of 1.3% isoflurane (a sub-minimal alveolar concentration, sub-MAC) for 6 h impaired recognition of novel objects from Day 1 to Day3 in adult mice. Prolonged sub-MAC isoflurane exposure also triggered typically reactive microglia and A1-like astrocytes in the hippocampus of adult mice on Day 3 after anesthesia. In addition, prolonged isoflurane inhalation switched microglia into a proinflammatory M1 phenotype characterized by elevated CD68 and iNOS as well as decreased arginase-1 and IL-10. Metformin pretreatment before anesthesia enhanced cognitive performance in the novel object test. The positive cellular modifications promoted by metformin pretreatment included the inhibition of reactive microglia and A1-like astrocytes and the polarization of microglia into M2 phenotype in the hippocampus of adult mice. In conclusion, prolonged sub-MAC isoflurane exposure triggered significant hippocampal neuroinflammation and cognitive decline in adult mice which can be alleviated by metformin pretreatment via inhibiting reactive microglia and A1-like astrocytes and promoting microglia polarization toward anti-inflammatory phenotype in the hippocampus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
International immunopharmacology - 109(2022) vom: 16. Aug., Seite 108903 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peng, Liangyu [VerfasserIn] |
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| Links: |
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| Themen: |
9100L32L2N |
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| Anmerkungen: |
Date Completed 21.06.2022 Date Revised 15.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2022.108903 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a With the widespread use of volatile anesthetic agents in the prolonged sedation for COVID-19 pneumonia and ARDS, there is an urgent need to investigate the effects and treatments of lengthy low-concentration inhaled anesthetics exposure on cognitive function in adults. Previous studies showed that general anesthetics dose- and exposure length-dependently induced neuroinflammatory response and cognitive decline in neonatal and aging animals. The anti-diabetes drug metformin has anti-neuroinflammation effects by modulating microglial polarization and inhibiting astrocyte activation. In this study, we demonstrated that the inhalation of 1.3% isoflurane (a sub-minimal alveolar concentration, sub-MAC) for 6 h impaired recognition of novel objects from Day 1 to Day3 in adult mice. Prolonged sub-MAC isoflurane exposure also triggered typically reactive microglia and A1-like astrocytes in the hippocampus of adult mice on Day 3 after anesthesia. In addition, prolonged isoflurane inhalation switched microglia into a proinflammatory M1 phenotype characterized by elevated CD68 and iNOS as well as decreased arginase-1 and IL-10. Metformin pretreatment before anesthesia enhanced cognitive performance in the novel object test. The positive cellular modifications promoted by metformin pretreatment included the inhibition of reactive microglia and A1-like astrocytes and the polarization of microglia into M2 phenotype in the hippocampus of adult mice. In conclusion, prolonged sub-MAC isoflurane exposure triggered significant hippocampal neuroinflammation and cognitive decline in adult mice which can be alleviated by metformin pretreatment via inhibiting reactive microglia and A1-like astrocytes and promoting microglia polarization toward anti-inflammatory phenotype in the hippocampus | ||
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| 700 | 1 | |a Fang, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Tianjiao |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Xiaoping |e verfasserin |4 aut | |
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