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.

Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis

“…Production of inflammatory related cytokines was also investigated to identify the M1/M2 phenotypic microglia from the viewpoint of functions. IL-6 has been considered an important pro-inflammatory cytokine in pathogenesis of POCD [ 37 ]. Furthermore, IL-6 is thought to be secreted specifically by M1 microglia [ 38 ].…”

Neuroprotective Effects against POCD by Photobiomodulation: Evidence from Assembly/Disassembly of the Cytoskeleton

“…17 IL-6 has been suggested as playing a crucial role in the neuroinflammatory response leading to POCD. 130 Inflammatory cytokines have also been associated with POCD after cardiac surgery 131 and levels of S-100, an indicator of traumatic brain injury, was found to be an indicator of POCD. 132,133 In addition, in a meta-analysis of studies investigating the inflammatory response of patients, IL-6 and S-100B were identified as being correlated with POCD.…”

Melatonin and Rapamycin Attenuate Isoflurane-Induced Cognitive Impairment Through Inhibition of Neuroinflammation by Suppressing the mTOR Signaling in the Hippocampus of Aged Mice

“…Animal studies demonstrated that the pathophysiological process of PND might be related to the inflammatory cytokines TNF-α, IL-1β, and IL-6 in the hippocampus (Tang et al, 2011; Hovens et al, 2014; Wang et al, 2017). The rodent experiments showed that the inhibition of the expression of central proinflammatory cytokine signaling can lower the severity of postoperative memory impairment (Cibelli et al, 2010; Terrando et al, 2010; Barrientos et al, 2012; Jiang et al, 2015). Further studies demonstrated that mTOR expression is vital in facilitating neuroinflammation in many neurodegenerative diseases (Soltani et al, 2018).…”