Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.