{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:08:23Z","timestamp":1789517303293,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Sevoflurane preconditioning (SPC) results in cerebral ischemic tolerance; however, the mechanism remains unclear. Promoting microglia\/macrophages polarization from pro\u2010inflammatory state to anti\u2010inflammatory phenotype has been indicated as a potential treatment target against ischemic stroke. In this study, we aimed to assess the effect of SPC on microglia polarization after stroke and which signaling pathway was involved in this transition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mouse primary microglia with SPC were challenged by oxygen\u2010glucose deprivation (OGD) or lipopolysaccharide (LPS), and mice with SPC were subjected to middle cerebral artery occlusion (MCAO). Then, the mRNA and protein levels of pro\u2010inflammatory\/anti\u2010inflammatory factors were analyzed. GSK\u20103\u03b2 phosphorylation and Nrf2 nuclear translocation were measured. The mRNA and protein expression of pro\u2010inflammatory\/anti\u2010inflammatory factors, neurological scores, infarct volume, cellular apoptosis, the proportion of pro\u2010inflammatory\/anti\u2010inflammatory microglia\/macrophages, and the generation of super\u2010oxidants were examined after SPC or GSK\u20103\u03b2 inhibitor TDZD treatment with or without Nrf2 deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sevoflurane preconditioning promoted anti\u2010inflammatory and inhibited pro\u2010inflammatory microglia\/macrophages phenotype both in vitro and in vivo. GSK\u20103\u03b2 phosphorylation at Ser9 was increased after SPC. Both SPC and TDZD administration enhanced Nrf2 nuclear translocation, reduced pro\u2010inflammatory microglia\/macrophages markers expression, promoted anti\u2010inflammatory markers level, and elicited a neuroprotective effect. Nrf2 deficiency abolished the promoted anti\u2010inflammatory microglia\/macrophages polarization and ischemic tolerance induced by TDZD treatment. The reduced percentage of pro\u2010inflammatory positive cells and super\u2010oxidants generation induced by SFC or TDZD was also reversed by Nrf2 knockdown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicated that SPC exerts brain ischemic tolerance and promotes anti\u2010inflammatory microglia\/macrophages polarization by GSK\u20103\u03b2\u2010dependent Nrf2 activation, which provides a novel mechanism for SPC\u2010induced neuroprotection.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13715","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T19:55:12Z","timestamp":1628538912000},"page":"1348-1365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Sevoflurane preconditioning protects experimental ischemic stroke by enhancing anti\u2010inflammatory microglia\/macrophages phenotype polarization through GSK\u20103\u03b2\/Nrf2 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