Nampt/RelB pathway protects learning and memory ability in aged rats after general anesthesia with sevoflurane and nitrous oxide

Anesthesia-induced postoperative cognitive dysfunction (POCD) has been confirmed in elderly patients, while studies have shown that NAMPT protein is critical for learning and memory. To better understand the mechanism of anesthesia-induced POCD, we studied the behavioral and biochemical changes in aged rats that were exposed to sevoflurane (Sev) and nitrous oxide (N₂O) for 4 hours. Rats were randomly divided into control group and anesthesia group. The anesthesia group rats were given 1.3% Sev and 50% N₂O for 4 hours, and controls with 50% O₂ for same time. Morris Water Maze test was used to test the rat's ability to learn and remember 24 hours exposure. The result shown that Sev-N₂O anesthesia induced a significant deficit in short-term spatial learning acquisition and memory retention, but it had no significant deficit in long-term. After 48 hours Sev-N₂O anesthesia, the neuronal Apoptosis and the expression of Bax, PARP-1 in hippocampus of rats increased significantly, and the expression of NAMPT, RelB decreased significantly. However, NAMPT activators could reduce the Apoptosis of hippocampal primary cells in vitro after 4 hours exposed with Sev-N₂O. Thus, we believed that down-regulation of NAMPT/RelB signaling was closely related to neuronal Apoptosis in the hippocampus contributed to the neurotoxicity and cognitive dysfunction induced by general anesthesia with sevoflurane-nitrous oxide.