Electroacupuncture ameliorates postoperative cognitive dysfunction and associated neuroinflammation via NLRP3 signal inhibition in aged mice

Background: Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA's regulatory role of inflammasomes remain unclear. Methods: The model of POCD was established by partial hepatectomy surgery in 18-month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL-1 beta and IL-6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF-kappa B pathway proteins were evaluated by western blotting. Results: EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL-1 beta and IL-6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO-1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF-kappa B was inhibited by EA, while NLRP3 activation abolished EA's treatment effects on cognitive function. Conclusion: EA alleviates POCD-mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA's treatment effects are dependent on NLRP3 inhibition.