Dong Ping, Zhao Jian, Li Ning, Lu Lingling, Li Liang, Zhang Xiyan, Yang Bo, Zhang Li, Li Dongliang
Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Anesthesiology, The People's Hospital of Chiping, Chiping, Shandong, China.
Behav Brain Res. 2018 Jul 16;347:325-331. doi: 10.1016/j.bbr.2018.03.031. Epub 2018 Mar 21.
Postoperative cognitive dysfunction is a common complication associated with anesthesia and surgery. Sevoflurane is a widely used volatile anesthetic in the clinical setting. Preclinical studies show that sevoflurane alone does not appear to cause cognitive dysfunction. Here, we examined whether sevoflurane induces cognitive decline under chronic intermittent hypoxia (CIH) conditions. Rats were exposed to CIH or control for 4 weeks. Two weeks after starting intermittent hypoxia, these animals underwent either 2.6% sevoflurane or vehicle exposure for 4 h. Four weeks after CIH, Morris Water Maze task showed that both groups of CIH rats exhibited significantly longer latency to locate the hidden platform and had shorter dwell-time in the goal quadrant compared with respective controls. Notably, CIH + sevoflurane rats had much higher latency and less dwell-time than CIH + vehicle rats. Molecular studies revealed that pro-inflammatory cytokine expression and activated microglia in the hippocampus were increased in both groups of CIH rats, with greater increases in CIH + sevoflurane rats. No differences in above measured parameters were observed between two control groups. Sevoflurane reduced PPAR-γ expression and activity in both control and CIH rats. Moreover, activated microglia was positively correlated with proinflammatory cytokine expression and negatively correlated with PPAR-γ expression and activity in CIH groups. The results suggest that microglia-mediated neuroinflammation in the hippocampus plays an important role in the pathogenesis of CIH-associated cognitive dysfunction, and that a moderate duration of sevoflurane exaggerates cognitive decline under CIH conditions by aggravating microglia-mediated neuroinflammation via downregulation of PPAR-γ in the hippocampus.
术后认知功能障碍是一种与麻醉和手术相关的常见并发症。七氟烷是临床环境中广泛使用的挥发性麻醉剂。临床前研究表明，单独使用七氟烷似乎不会导致认知功能障碍。在此，我们研究了七氟烷在慢性间歇性缺氧（CIH）条件下是否会诱导认知功能下降。将大鼠暴露于CIH或对照组4周。开始间歇性缺氧两周后，这些动物接受2.6%七氟烷或载体暴露4小时。CIH四周后，莫里斯水迷宫任务显示，与各自的对照组相比，两组CIH大鼠定位隐藏平台的潜伏期显著延长，在目标象限的停留时间缩短。值得注意的是，CIH+七氟烷组大鼠的潜伏期比CIH+载体组大鼠长得多，停留时间也更短。分子研究表明，两组CIH大鼠海马中的促炎细胞因子表达和活化小胶质细胞均增加，CIH+七氟烷组大鼠的增加更为明显。两个对照组之间在上述测量参数上未观察到差异。七氟烷降低了对照组和CIH大鼠中PPAR-γ的表达和活性。此外，在CIH组中，活化的小胶质细胞与促炎细胞因子表达呈正相关，与PPAR-γ表达和活性呈负相关。结果表明，海马中小胶质细胞介导的神经炎症在CIH相关认知功能障碍的发病机制中起重要作用，并且在CIH条件下，适度时长的七氟烷通过下调海马中的PPAR-γ加重小胶质细胞介导的神经炎症，从而加剧认知功能下降。
