Graded surgical stress reveals postoperative behavioral changes associated with systemic oxidative stress

Postoperative delirium (POD) is a postoperative complication characterized by acute-onset attention deficits and cognitive impairment following surgery. Recently, oxidative stress has been increasingly recognized in its pathogenesis. This study investigated the relationship between postoperative behavioral changes and systemic oxidative stress responses under graded levels of surgical stress. Male C57BL/6J mice were divided into three groups: anesthesia alone, standard laparotomy, and open surgery with added localized thermal injury (OPT). The buried food test was performed 24 h after anesthesia induction to evaluate search latency. Serum was collected after the behavioral test to measure derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), and the BAP/d-ROMs ratio. Search latency became more prolonged under conditions of increased surgical invasiveness. The d-ROMs values increased progressively with increasing surgical stress, whereas the BAP/d-ROMs ratio progressively decreased. Group-stratified and interaction analyses suggested that the relationship between postoperative behavioral changes and systemic oxidative stress responses differed according to the degree of surgical invasiveness, particularly regarding the BAP/d-ROMs ratio. These findings suggest that oxidative stress responses may contribute differently to postoperative behavioral changes under different levels of graded surgical stress.