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The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats.
J Surg Res. 2012 Nov;178(1):e1-8
Authors: Peng M, Wang YL, Wang FF, Chen C, Wang CY
Abstract
BACKGROUND: Neuroinflammatory response triggered by surgery has been increasingly reported to be associated with postoperative cognitive dysfunction. Proinflammatory cytokines, such as interleukin 1? (IL-1?) and tumor necrosis factor ? (TNF-?), 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-1? and TNF-? 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-1? and TNF-? expression through downregulation of the COX-2/PGE2 pathway.
CONCLUSION: 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.
PMID: 22959208 [PubMed - indexed for MEDLINE]
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