Inhibiting tumor necrosis factor-α signaling attenuates postoperative cognitive dysfunction in aged rats.

Abstract

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 pro-inflammatory cytokines, including TNF-α, interleukin (IL)-1β, IL-4 and IL-6 in the hippocampal tissues. However, intracisternal administration of the TNF-α receptor antagonist, R-7050, during surgery attenuated these defects in cognitive function and inhibited the production of the pro-inflammatory cytokines in the hippocampal tissues. Furthermore, intracisternal administration of R-7050 inhibited the activation of the downstream nuclear factor-κB and mitogen-activated protein kinase signaling pathway in the hippocampal tissues. Therefore, the results of the present study suggested a key role of the TNF-α-mediated signaling pathway in the development of POCD.