Sevoflurane and lipopolysaccharide-induced inflammation differentially affect γ-aminobutyric acid type A receptor-mediated tonic inhibition in the hippocampus of male mice

Editor—Increasing evidence suggests that inflammation and exposure to general anaesthetic drugs trigger long-lasting changes in brain function that may contribute to perioperative neurocognitive disorders. 1 Vutskits L. Xie Z. Lasting impact of general anaesthesia on the brain: mechanisms and relevance. Nat Rev Neurosci. 2016; 17: 705-717 Crossref PubMed Scopus (313) Google Scholar ,2 Eckenhoff R.G. Maze M. Xie Z. et al. Perioperative neurocognitive disorder: state of the preclinical science. Anesthesiology. 2020; 132: 55-68 Crossref PubMed Scopus (82) Google Scholar Interestingly, an interplay between inflammation and general anaesthetic drugs may be important in the development of these disorders. Preclinical studies have shown that the combination of inflammation (induced by lipopolysaccharide [LPS]) followed by exposure to a general anaesthetic drug (either etomidate or sevoflurane) causes cognitive deficits that are not observed after treatment with LPS or the anaesthetic drug alone. 3 Khodaei S. Wang D.S. Ariza A. Syed R.M. Orser B.A. The impact of inflammation and general anesthesia on memory and executive function in mice. Anesth Analg. September 30, 2022; https://doi.org/10.1213/ANE.0000000000006221 Crossref PubMed Scopus (3) Google Scholar ,4 Useinovic N. Maksimovic S. Liechty C. Cabrera O.H. Quillinan N. Jevtovic-Todorovic V. Systemic inflammation exacerbates developmental neurotoxicity induced by sevoflurane in neonatal rats. Br J Anaesth. 2022; 129: 555-566 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Understanding the cellular mechanisms underlying this interaction is important, as such insights might lead to novel treatments for perioperative neurocognitive disorders. One potential mechanism is disruption of inhibitory neurotransmission, which occurs after both inflammation and general anaesthesia. 5 Wang D.S. Zurek A.A. Lecker I. et al. Memory deficits induced by inflammation are regulated by α5-subunit-containing GABAA receptors. Cell Rep. 2012; 2: 488-496 Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar , 6 Jiang J. Tang B. Wang L. et al. Systemic LPS-induced microglial activation results in increased GABAregic tone: a mechanism of protection against neuroinflammation in the medial prefrontal cortex in mice. Brain Behav Immun. 2022; 99: 53-69 Crossref PubMed Scopus (22) Google Scholar , 7 Zurek A.A. Yu J. Wang D.S. et al. Sustained increase in α5GABAA receptor function impairs memory after anesthesia. J Clin Invest. 2014; 124: 5437-5441 Crossref PubMed Scopus (116) Google Scholar