{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:04:57Z","timestamp":1784088297042,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Isoflurane\u2010induced neuroinflammation triggers cognitive impairment in aged mice, but its underlying mechanism remains unclear. This study investigated the molecular mechanism by which isoflurane promotes glycolytic reprogramming to cause cognitive dysfunction in aged mice and identified potential therapeutic targets. 18\u2010month\u2010old mice were placed in an anaesthetic induction chamber containing 2% isoflurane (ISO) for 2\u2009h to induce anaesthesia; this procedure was repeated daily for 5\u2009days to establish a model of age\u2010related cognitive impairment in mice. Behavioural studies in mice were conducted using the Y\u2010Maze, contextual fear conditioning test (CFCT), Novel Object Recognition (NOR) test, and water maze test. Immunofluorescence analysis was employed to detect changes in the expression of microglia\u2010related proteins PGK1, Hip, iNOS, Arg1, and P65. RT\u2010PCR was employed to detect changes in mRNA expression levels of GLUT2, PKM2, HK2, and LDHA, which are associated with cellular metabolic reprogramming. ELISA was used to measure alterations in TNF\u2010\u03b2, IL\u20104, IL\u201010, IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1 cytokines. ISO enhanced glycolytic flux via PGK1, thereby driving microglia polarization toward the pro\u2010inflammatory M1 phenotype and triggering neuroinflammation, ultimately leading to cognitive impairment in mice. Supplementing the glycolytic intermediate FBP reversed the anti\u2010inflammatory effects induced by PGK1 knockdown, confirmed that PGK1 exerted its effects through the \u201cPGK1\u2010glycolysis axis.\u201d Mechanistically, PGK1 knockdown effectively suppressed M1 polarization of microglia while promoting their transition to the anti\u2010inflammatory M2 phenotype. This significantly mitigated ISO\u2010induced neuroinflammation and neuronal injury, ultimately improving cognitive function in mice. These findings reveal that PGK1 serves as a key molecular link between ISO anaesthesia and neuroinflammatory cognitive impairment. Targeting and inhibiting PGK1 exerts neuroprotective effects by reprogramming microglial glucose metabolism and phenotype, providing novel theoretical insights and potential therapeutic strategies for preventing ISO\u2010induced neurological complications.<\/jats:p>","DOI":"10.1111\/jcmm.71276","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:14:37Z","timestamp":1783059277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PGK1<\/scp>\n                    Drives Glial Glycolytic Reprogramming to Mediate Isoflurane\u2010Induced Cognitive Impairment in Aged Mice"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-5106","authenticated-orcid":false,"given":"Zhuo","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Beijing Chao\u2010Yang Hospital, Capital Medical University  Beijing 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