Abstract
Postoperative cognitive dysfunction (POCD) is commonly observed in perioperative care following major surgery and general anesthesia in elderly individuals. No preventive or interventional agents have been established so far. Although the role of interleukin-1β (IL-1β)-mediated neuroinflammation following surgery and anesthesia is strongly implicated in POCD, the exact mechanism of action remains to be explored. Growing evidence has shown that mitochondria-derived reactive oxygen species (mtROS) are closely linked to IL-1β expression through a redox sensor known as the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. Therefore, we hypothesize that the mechanisms underlying POCD involve the mtROS/NLRP3 inflammasome/IL-1β signaling pathway. Furthermore, we speculate that cholinergic anti-inflammatory pathway induced by α7 nicotinic acetylcholine receptor (a7nAChR) may be the potential upstream of mtROS/NLRP3 inflammasome/IL-1β signaling pathway in POCD. For validating the hypotheses, we provide experimental plan involving different paradigms namely; microglial cells and behavioral studies. The link between mtROS, the NLRP3 inflammasome, and IL-1β within and between these different stages in combination with mtROS and NLRP3 inflammasome agonists and inhibitors could be explored using techniques, such as knockout mice, small interference ribonucleic acid, flow cytometry, co-immunoprecipitation, and the Morris Water Maze test. We conclude that the NLRP3 inflammasome is a new preventive and therapeutic target for POCD.
Highlights
Postoperative cognitive dysfunction (POCD) is a highly prevalent condition with significant effects on the prognosis of elderly patients undergoing surgery, experiencing problems with memory, concentration, information processing, language comprehension, and social integration that can last for months or may even be permanent (Leslie, 2017)
The hypothesis we present here is that mitochondria-derived reactive oxygen species (mtROS)-induced nod-like receptor pyrin domain-containing 3 (NLRP3) activation may be a pivotal upstream mechanism that controls microglial IL-1β cleavage and secretion, and subsequent IL-1β-mediated inflammatory cascades in the hippocampus
The activation of microglia induced by surgery and the resulting exacerbated inflammatory response in the hippocampus have been associated with impaired cognitive function (Hovens et al, 2014)
Summary
Postoperative cognitive dysfunction (POCD) is a highly prevalent condition with significant effects on the prognosis of elderly patients undergoing surgery, experiencing problems with memory, concentration, information processing, language comprehension, and social integration that can last for months or may even be permanent (Leslie, 2017). Recent studies have revealed that isoflurane-induced cognitive impairment was associated with high levels of NLRP3 in the hippocampus of aged mice and the impairment was reversed by the inhibition of NLRP3-caspase-1 pathway (Wang et al, 2018). The hypothesis we present here is that mtROS-induced NLRP3 activation may be a pivotal upstream mechanism that controls microglial IL-1β cleavage and secretion, and subsequent IL-1β-mediated inflammatory cascades in the hippocampus.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.