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Inhibiting tumor necrosis factorα signaling attenuates postoperative cognitive dysfunction in aged rats

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Postoperative cognitive dysfunction (POCD), commonly observed in elderly patients, is characterized by impaired concentration, memory and learning following surgery, and may persist for a long duration or progress into serious central nervous system diseases. It has been demonstrated neuroinflammation caused by surgery is involved in the development of POCD. However, the detailed molecular mechanism remains to be fully elucidated. The present study aimed to reveal the role of tumor necrosis factor (TNF)α in the development of POCD in aged rats. Laparotomy was performed to mimic human abdominal surgery in the aged rats. Following surgery, the memory and learning functions were impaired, with significant upregulation of proinflammatory cytokines, including TNFα, interleukin (IL)1β, IL4 and IL6 in the hippocampal tissues. However, intracisternal administration of the TNFα receptor antagonist, R7050, during surgery attenuated these defects in cognitive function and inhibited the production of the proinflammatory cytokines in the hippocampal tissues. Furthermore, intracisternal administration of R7050 inhibited the activation of the downstream nuclear factorκB and mitogenactivated protein kinase signaling pathway in the hippocampal tissues. Therefore, the results of the present study suggested a key role of the TNFαmediated signaling pathway in the development of POCD.
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Document Type: Research Article

Affiliations: 1: Department of Anesthesiology, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China 2: Department of Anesthesiology, China Meitan General Hospital, Beijing 100028, P.R. China 3: Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong 253045, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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