Intracisternal administration of an interleukin-6 receptor antagonist attenuates surgery-induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats

摘要

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.