title: Intracisternal administration of an interleukin-6 receptor antagonist attenuates surgery-induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats.
abstract: Postoperative cognitive dysfunction (POCD) is common in elderly patients, and may persist or even evolve into Alzheimer's disease. It has been hypothesized that POCD is mediated by surgery-induced inflammatory processes. As a pro-inflammatory cytokine, the detailed role of interleukin (IL)-6 in POCD remains largely unknown. In this study, laparotomy was used to mimic human abdominal surgery in aged Sprague-Dawley rats. It was found that memory and learning were impaired following surgery, accompanied by the significant upregulation of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α), IL-1β, IL-4, and IL-6. Moreover, the intracisternal administration of the IL-6 receptor (IL-6R) antagonist (tocilizumab, also know as MRA) at the time of surgery notably attenuated the surgery-induced cognitive deficit, and significantly inhibited the upregulated expression of pro-inflammatory cytokines. Further investigation indicated that the intracisternal administration of MRA inhibited the activation of the NF-κB signaling pathway in aged rats following surgery. In summary, the findings of this study suggest that IL-6 plays a crucial role in POCD, and that IL-6R antagonists may serve as novel agents for the prevention or treatment of POCD.
authors: Department of Anesthesiology, Huizhou Municipal Central Hospital, Huizhou, Guangdong 516001, P.R. China.
authors: Peng
authors: P
authors: Jiang
authors: Department of Anesthesiology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong 510010, P.R. China.
authors: Qiong
authors: Q
authors: Ling
authors: Department of Anesthesiology, Huizhou Municipal Central Hospital, Huizhou, Guangdong 516001, P.R. China.
authors: Hongbo
authors: H
authors: Liu
authors: Department of Anesthesiology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong 510010, P.R. China.
authors: Weifeng
authors: W
authors: Tu
keywords: aged; interleukin-6; neuroinflammation; postoperative cognitive dysfunction