Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3β (pSer9-GSK3β) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.

中文翻译：

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高浓度的依达拉奉可减轻老年小鼠全身麻醉下腹部手术引起的认知功能障碍。

术后认知功能障碍（POCD）是一种影响老年患者术后的常见神经系统疾病。不幸的是，尚未发现该疾病的有效治疗方法。据报道，依达拉奉（Edaravone）（一种临床上使用的自由基清除剂）的剂量为3 mg / kg，可防止成年啮齿类动物因手术和脂多糖的结合而诱发神经炎症。但是，我们发现依达拉奉在如此低的浓度下不能抑制老年小鼠的POCD。取而代之的是，在异氟烷全身麻醉下进行腹部手术的14个月大小鼠中，依达拉奉33.2 mg / kg可以显着预防识别和空间认知功能障碍。此外，依达拉奉显着预防了老年小鼠腹部手术引起的肿瘤坏死因子-α（TNF-α），白介素-1β（IL-1β）和白介素-6（IL-6）的增加。依达拉奉还可以减少手术小鼠海马区的神经胶质纤维酸性蛋白（GFAP）和离子钙结合适配器分子1（Iba-1）阳性区域，提示依达拉奉可能抑制手术引起的小胶质细胞和星形胶质细胞过度活化。此外，依达拉奉（Western blotting）证实实质上增加了PSD-95和pSer9-糖原合酶激酶-3β（pSer9-GSK3β）的表达。此外，依达拉奉组小鼠的乙酰胆碱酯酶（AChE）活性降低。所有这些结果表明，高浓度的依达拉奉可能抑制衰老动物手术引起的认知障碍，可能是由于神经炎症的减弱，突触蛋白的增加以及胆碱能传递的升高，