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

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.