title: Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE.
abstract: BACKGROUND
  Postoperative 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.
  
  
  METHODS
  Old 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  These data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Li
authors.forename: Zong-Ze
authors.initials: ZZ
authors.lastname: Zhang
authors.forename: Mian
authors.initials: M
authors.lastname: Peng
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Jun-Jian
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Cheng-Yao
authors.initials: CY
authors.lastname: Wang
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000375:Aging / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000276:immunology; D003072:Cognition Disorders / Q000209:etiology / Q000276:immunology*; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D006498:Hepatectomy / Q000009:adverse effects; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D009443:Neuritis / Q000209:etiology / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology; D011183:Postoperative Complications / Q000209:etiology / Q000276:immunology*; D011897:Random Allocation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000276:immunology* / Q000378:metabolism
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D053583:Interleukin-1beta; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse
keywords: High mobility group box-1; Neuroinflammation; Postoperative cognitive dysfunction; Receptor for advanced glycation end products; S100B