This study evaluated the effect of epigallocatechin-3-gallate (EGCG), a flavonoid, on postoperative cognitive dysfunction by modulating microglial phenotype expression in aged rats following general anesthesia with isoflurane. Eighteen-month-old male Sprague–Dawley rats were randomly assigned to the EGCG and control groups. EGCG in distilled water (DW) or DW alone was administered orally for 7 days before anesthesia. After anesthesia, cognitive function was assessed using the Y-maze test, and neuronal damage was evaluated histologically. Microglial activation and phenotype differentiation were also analyzed. At 24 h after anesthesia, the alternation ratio was significantly higher in the EGCG group than in the control group (70.00 ± 7.98% vs. 28.14 ± 11.52%, p < 0.001). The EGCG group exhibited reduced neuronal damage and microglial activation. Additionally, M1 phenotype activation was significantly lower (30.03 ± 7.73% vs. 51.00 ± 9.83%, p < 0.001), and M2 phenotype activation was significantly higher (17.61 ± 5.52% vs. 5.99 ± 2.46%, p < 0.001) in the EGCG group than in the control group. In summary, pre-anesthetic administration of EGCG modulated microglial phenotype differentiation, reduced neuronal damage, and improved postoperative cognitive function in aged rats following general anesthesia.
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