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Microglial metabolic reprogramming, a pivotal aspect of the immune\u2010inflammatory response, modulates microglia\u2013neuron interactions and postoperative cognitive function through microenvironmental alterations. Aberrant overexpression of RUVBL2 disrupts metabolic homeostasis, leading to stress granule (SG) aggregation and fibrosis. This study investigated the role of RUVBL2 in regulating metabolic reprogramming to mediate SG formation, with the aim of identifying novel prognostic targets for inhibiting glycolysis and mitigating POD\u2010induced MCI progression. A POD model was established in aged MCI rats using 3% sevoflurane anesthesia for 3\u2009h, combined with open reduction and internal fixation (ORIF). Multimodal magnetic resonance imaging (MRI) was employed to assess postoperative cognitive function. Glycolytic and oxidative phosphorylation (OXPHOS) activities in primary hippocampal microglia were quantified by extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Lentiviral\u2010mediated RUVBL2 expression modulation was performed to verify its role in microglial metabolic reprogramming. Postoperative hippocampal microglia underwent metabolic reprogramming from OXPHOS to glycolysis, with RUVBL2 expression correlating positively with POD progression. Elevated RUVBL2 expression drove metabolic reprogramming, while RUVBL2 knockdown inhibited this process, alleviated pro\u2010inflammatory microglia\u2010induced neuroinflammation and SG aggregation, and improved spontaneous neural activity and hippocampus\u2010dependent cognitive deficits. In primary hippocampal microglia, RUVBL2 knockdown enhanced OXPHOS\u2010related OCR and reduced glycolysis\u2010associated ECAR, producing a synergistic neuroprotective effect. These findings reveal the critical role of RUVBL2 in regulating POD, highlight metabolic reprogramming as a novel therapeutic target, and suggest RUVBL2 as a promising intervention strategy for POD.<\/jats:p>","DOI":"10.1111\/acel.70458","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T15:25:01Z","timestamp":1775229901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RUVBL2<\/scp>\n                    Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative Delirium in Aged Mild Cognitive Impairment Rats"],"prefix":"10.1111","volume":"25","author":[{"given":"Lin","family":"Zhang","sequence":"first","affiliation":[{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"},{"name":"Department of Anesthesiology Tianjin University Central Hospital  Tianjin China"},{"name":"Department of 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