Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.

术后谵妄（POD）是老年患者中常见且严重的神经精神综合征，缺乏有效的治疗方法。 Omega-3 脂肪酸具有抗炎和抗氧化特性，在多种疾病中显示出有效的神经保护作用。本研究调查了 omega-3 脂肪酸是否可以对老年小鼠的 POD 发挥神经保护作用。建立POD小鼠模型，通过评估老年小鼠不同时间点的全身炎症变化、神经炎症、氧化应激和行为，探讨omega-3脂肪酸在剖腹手术诱导的谵妄样行为中的作用。术前口服 omega-3 脂肪酸（300 mg/kg）3 周，可显着减轻麻醉/手术诱导的 POD 样行为以及老年小鼠外周血中促炎细胞因子的积累。此外，它还显着减轻了手术小鼠前额皮质和海马的神经炎症和氧化应激反应（丙二醛 [MDA] 和超氧化物歧化酶 [SOD]）。我们的研究结果证明，omega-3 脂肪酸预处理可能通过其抗炎和抗氧化作用机制在 POD 治疗中发挥至关重要的作用，这可能是老年患者 POD 的一种有前途的预防策略。