Prophylactic Effects of Sub-anesthesia Ketamine on Cognitive Decline, Neuroinflammation, and Oxidative Stress in Elderly Mice

亚麻醉氯胺酮对老年小鼠认知能力下降、神经炎症和氧化应激的预防作用

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作者:Minmin Chen, Yinqiu Han, Bin Que, Rong Zhou, Jianhui Gan, Xiaoyun Dong

Abstract

Cognitive dysfunction is a very common postoperative complication. The study aimed at investigating the effects of ketamine on the cognition of elderly mice after anesthesia and surgery (AS). We reported that AS impaired the cognition of elderly mice, while ketamine helped to maintain the cognitive function. Ketamine decreased the levels of TNF-α, IL-6, IL-1β and the expression of p-TAU, S100B in hippocampal induced by AS. In addition, AS triggered severe oxidative stress in hippocampal, while ketamine inhibited it. Oxidative stress induced autophagy of hippocampal neurons via inhibiting PI3K/AKT/mTOR pathway. Ketamine could activate PI3K pathway and inhibit autophagy in hippocampal, thus maintain the loss of hippocampal neurons. The study suggested that ketamine inhibited the neuroinflammation and oxidative stress, reduced the autophagy of hippocampal neurons via PI3K/AKT/mTOR pathway. It may provide novel methods for the protection of cognitive function in elderly during perioperative period.

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