Dexmedetomidine alleviates hippocampal neuronal loss and cognitive decline in rats undergoing open surgery under sevoflurane anaesthesia by suppressing CCAAT/enhancer‐binding protein beta

Abstract

AbstractDexmedetomidine (Dex) may exert neuroprotective effects by attenuating inflammatory responses. However, whether Dex specifically improves postoperative cognitive dysfunction (POCD) by inhibiting microglial inflammation through what pathway remains unclear. In this study, the POCD model was constructed by performing open surgery after 3 h of continuous inhalation of 3% sevoflurane to rats, which were intraperitoneally injected with 25 μg/kg Dex .5 h before anaesthesia. The results displayed that Dex intervention decreased rat escape latency, maintained swimming speed and increased the number of times rats crossed the platform and the time spent in the target quadrant. Furthermore, the rat neuronal injury was restored, alleviated POCD modelling‐induced rat hippocampal microglial activation and inhibited microglial M1 type polarization. Besides, we administered Dex injection and/or CCAAT/enhancer‐binding protein beta (CEBPB) knockdown on the basis of sevoflurane exposure and open surgery and found that CEBPB was knocked down, resulting in the inability of Dex to function, which confirmed CEBPB as a target for Dex treatment. To sum up, Dex improved POCD by considering CEBPB as a drug target to activate the c‐Jun N‐terminal kinase (JNK)/p‐38 signaling pathway, inhibiting microglial M1 polarization‐mediated inflammation in the central nervous system.