Relationship between inflammatory responses induced by perioperative infection and surgical stress and postoperative cognitive dysfunction in mice

Objective To evaluate the relationship between inflammatory responses induced by perioperative infection and surgical stress and postoperative cognitive dysfunction in mice. Methods One hundred forty-four healthy male C57BL/6 mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups (n=36 each) using a random number table: control group (group C), surgery group (group S), infection group (group I), and infection + surgery group (group I+ S). In group S, the open reduction and internal fixation was performed after tibial fracture was induced.Lipopolysaccharide (LPS) 100 μg/kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery in group I. In group I+ S, LPS 100 μg/kg was injected intraperitoneally at the same time every day for 5 consecutive days starting from 1 day before surgery, and the open reduction and internal fixation was performed after tibial fracture was induced at 2 h after LPS injection on the day of surgery.Contextual fear conditioning test was performed on 1 and 3 days after surgery, and cognitive function was assessed.The rate of freezing time was calculated.The peripheral venous blood samples were collected for determination of plasma interleukin-6 (IL-6) and IL-1β concentrations by enzyme-linked immunosorbent assay.The animals were then sacrificed, and the hippocampi were isolated for determination of IL-6, IL-1β and prostaglandin E2 (PGE2) contents in hippocampal tissues by enzyme-linked immunosorbent assay. Results Compared with group C, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the contents of IL-6, IL-1β and PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in S and I+ S groups, the concentrations of plasma IL-6 and IL-1β were significantly increased on 1 day after surgery, and the concentration of plasma IL-1β was significantly increased on 3 days after surgery in group S, the concentrations of plasma IL-6 and IL-1β were significantly increased on 1 and 3 days after surgery in I and I+ S groups (P 0.05). Compared with group S or group I, the rate of freezing time was significantly decreased on 1 and 3 days after surgery, and the concentrations of IL-6 and IL-1β in plasma and contents of IL-6, IL-1β and PGE2 in hippocampal tissues were significantly increased on 1 and 3 days after surgery in group I+ S (P<0.01). Conclusion Inflammatory responses induced by perioperative infection and surgical stress can aggravate postoperative cognitive dysfunction in mice. Key words: Bacterial infections; Intraoperative period; Stress; Inflammation; Cognition disorders; Postoperative complications