Hippocampal complement C3 might contribute to cognitive impairment induced by anesthesia and surgery

Postoperative cognitive dysfunction is a well-recognized complication after major surgery in the elderly, but its pathophysiological mechanism is not fully understood. In the present study, we used liquid chromatography-tandem mass spectrometry combined with tandem mass tags to identify differentially expressed proteins and perform further functional studies on protein of interest. Here, we showed that hippocampal complement C3 was significantly upregulated after surgery, which was accompanied by marked decreases in synaptic related proteins and density. In aged patients undergoing gastrointestinal surgery, we also found significantly increased plasma level of C3b postoperatively and were negatively associated with cognitive performance. Notably, selective inhibition of complement C3 by compstatin was able to rescue synaptic and cognitive impairments induced by surgery in aged mice. Collectively, our study confirms that surgery can induce cognitive impairments, and the possible mechanisms might be related to abnormal complement signaling and synaptic disruption.