Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE

Abstract

BackgroundPostoperative cognitive dysfunction, a common complication after surgery in elderly patients, is an increasing and largely underestimated problem without a defined etiology. Neuroinflammation plays an important role in the pathogenesis of postoperative cognitive dysfunction. The present study sought to investigate the role of neuroinflammation mediated by high-mobility group box 1 (HMGB1), S100B, and the receptor for advanced glycation end product (RAGE) in cognitive dysfunction after partial hepatectomy in aged mice. Materials and methodsOld C57BL/6 mice were randomly divided into three groups: normal control (n = 18), anesthetic (n = 66), and surgery (n = 66). The mice in the surgery or anesthetic group received isoflurane anesthesia for either partial hepatectomy or no surgery, respectively. Cognitive function was subsequently assessed using a Y-maze. HMGB1, S100B, RAGE, interleukin-1β, and nuclear factor-kappaB p65 levels were measured at 12 h and 1, 3, and 7 d after surgery. Immunofluorescence double labeling was performed to study the colocalization between RAGE and its ligands, HMGB1 and S100B. ResultsThe mice’s learning and memory abilities were significantly impaired at 1 and 3 d and 2 and 4 d after surgery, respectively. The expression of HMGB1, S100B, RAGE, and nuclear factor-kappaB p65 had increased significantly at 12 h and 1 and 3 d after surgery. The interleukin-1β level was significantly increased at 1 and 3 d after surgery. The interaction of HMGB1 or S100B with RAGE was confirmed at 1 d after surgery. ConclusionsThese data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.