title: The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats.
abstract: BACKGROUND
  Neuroinflammatory response triggered by surgery has been increasingly reported to be associated with postoperative cognitive dysfunction. Proinflammatory cytokines, such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α), play a pivotal role in mediating surgery-induced neuroinflammation. The role of cyclooxygenase-2 (COX-2), a critical regulator in inflammatory response, in surgery-induced neuroinflammation is still unknown. The aim of the study was to investigate the changes of COX-2 expression and prostaglandin E2 (PGE2) production in the hippocampus in aged rats following partial hepatectomy. The effects of selective COX-2 inhibitor (parecoxib) on hippocampal proinflammatory cytokine expression were also evaluated.
  
  
  METHODS
  Aged rats were randomly divided into three groups: control (n = 10), surgery (n = 30), and parecoxib (n = 30). Control animals received sterile saline to control for the effects of injection stress. Rats in the surgery group received partial hepatectomy under isoflurane anesthesia and sterile saline injection. Rats in the parecoxib group received surgery and anesthesia similar to surgery group rats, and parecoxib treatment. On postanesthetic days 1, 3, and 7, animals were euthanized to assess levels of hippocampal COX-2 expression, PGE2 production, and cytokines IL-1β and TNF-α expression. The effects of parecoxib on proinflammatory cytokine expression were also assessed.
  
  
  RESULTS
  Partial hepatectomy significantly increased COX-2 expression, PGE2 production, and proinflammatory cytokine expression in the hippocampus in aged rats on postoperative days 1 and 3. Parecoxib inhibited hippocampal IL-1β and TNF-α expression through downregulation of the COX-2/PGE2 pathway.
  
  
  CONCLUSIONS
  COX-2 may play a critical role in surgery-induced neuroinflammation. The COX-2 inhibitor may be a promising candidate for treatment of neuroinflammation caused by surgical trauma.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China. sophie_pm@msn.com
authors.forename: Mian
authors.initials: M
authors.lastname: Peng
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.forename: Cheng-Yao
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy / Q000517:prevention & control*; D015870:Gene Expression / Q000276:immunology; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000601:surgery; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; C409945:parecoxib; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone