脓毒症相关脑病（SAE）是脓毒症最常见的并发症，发病率和死亡率增加。迄今为止，仍然没有既定的药物治疗方法。美金刚作为一种 NMDA（N-甲基-d-天冬氨酸）受体拮抗剂，对许多疾病中的认知和情绪功能障碍具有神经保护作用。我们进行盲肠结扎穿刺 (CLP) 诱导败血症作为 SAE 的理想动物模型。通过胃内给药对 CLP 诱导的脓毒症小鼠进行美金刚治疗。新的物体识别测试表明，美金刚显着改善脓毒症小鼠的认知功能障碍。旷场试验显示，美金刚可缓解脓毒症小鼠的焦虑样行为和运动能力。杆测试进一步证实了美金刚对不动的保护作用。美金刚显着抑制脓毒症后第一天和第七天的过量谷氨酸产生并改善受损的神经发生，同时减少促炎细胞因子的产生（肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β（IL-1β）和IL） -10) 和 SAE 大脑中小胶质细胞的激活。此外，美金刚治疗还可通过抑制金属蛋白酶-9 (MMP-9) 的表达来减少脓毒症引起的脑血屏障破坏。总之，美金刚对认知和情绪缺陷具有神经保护作用，这可能被认为是 SAE 的一种有前途的疗法。© 2023 作者。由美国化学会出版。

Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (N-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE.© 2023 The Authors. Published by American Chemical Society.