Bridging the Gap: Investigating the Link between Inflammasomes and Postoperative Cognitive Dysfunction

Abstract

Postoperative cognitive dysfunction (POCD) is a cluster of cognitive problems that may arise after surgery. POCD symptoms include memory loss, focus inattention, and communication difficulties. Inflammasomes, intracellular multiprotein complexes that control inflammation, may have a significant role in the development of POCD. It has been postulated that the NLRP3 inflammasome promotes cognitive impairment by triggering the inflammatory response in the brain. Nevertheless, there are many gaps in the current literature to understand the underlying pathophysiological mechanisms and develop future therapy. This review article underlines the limits of our current knowledge about the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome and POCD. We first discuss inflammasomes and their types, structures, and functions, then summarize recent evidence of the NLRP3 inflammasome's involvement in POCD. Next, we propose a hypothesis that suggests the involvement of inflammasomes in multiple organs, including local surgical sites, blood circulation, and other peripheral organs, leading to systemic inflammation and subsequent neuronal dysfunction in the brain, resulting in POCD. Research directions are then discussed, including analyses of inflammasomes in more clinical POCD animal models and clinical trials, studies of inflammasome types that are involved in POCD, and investigations into whether inflammasomes occur at the surgical site, in circulating blood, and in peripheral organs. Finally, we discuss the potential benefits of using new technologies and approaches to study inflammasomes in POCD. A thorough investigation of inflammasomes in POCD might substantially affect clinical practice.

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies

“…The NLRP3 inflammasome, comprising the NLRP3 protein, pro-caspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC), mediates neuroinflammation that not only directly contributes to the POCD but is also closely associated with high-risk factors for POCD ( Li et al, 2022 ). NLRP3 inflammasome activation occurs in two steps: initiation and activation ( Zhang et al, 2023 ). During the initiation step, cytokine signals stimulate cytokine receptors or TLRs, leading to NF-κB translocation and the promotion of NLRP3 and pro-IL-1β (immature form of inflammatory cytokine) transcription.…”

Nanomaterial-Based Strategies for Attenuating T-Cell-Mediated Immunodepression in Stroke Patients: Advancing Research Perspectives

“…[1][2][3] In addition to the acute damage caused by the initial ischemic event, stroke triggers a complex cascade of secondary processes, including neuroinflammation, immune cell activation, and immunodepression. [4][5][6][7][8][9][10] Among the immune cells involved in the poststroke immune response, T cells have emerged as key players in modulating the inflammatory environment and influencing stroke outcomes. [11][12][13] T-cell-mediated immunodepression refers to the functional impairment and reduced immune response observed in T cells following stroke.…”