Anesthesiology Department, Zhejiang Chinese Medical University, Hangzhou, China.
Anesthesiology Department, The Second Hospital of Jiaxing, The Second Affiliated Hospital of Jiaxing University, Jiaxing Key Laboratory of Basic Research and Clinical Transformation of Perioperative Precision Anesthesia, Jiaxing, China.
Aging Dis. 2023 Dec 1;14(6):1981-2002. doi: 10.14336/AD.2023.0501.
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.
术后认知功能障碍(POCD)是一组手术后可能出现的认知问题。POCD 症状包括记忆力减退、注意力不集中和沟通困难。炎性小体是控制炎症的细胞内多蛋白复合物,可能在 POCD 的发展中起重要作用。有人假设 NLRP3 炎性小体通过触发大脑中的炎症反应促进认知障碍。然而,目前的文献中有许多空白需要了解潜在的病理生理机制并开发未来的治疗方法。这篇综述文章强调了我们目前对 NLRP3(NOD、LRR 和 pyrin 结构域蛋白 3)炎性小体和 POCD 的了解的局限性。我们首先讨论了炎性小体及其类型、结构和功能,然后总结了最近关于 NLRP3 炎性小体参与 POCD 的证据。接下来,我们提出了一个假设,即炎性小体参与包括局部手术部位、血液循环和其他外周器官在内的多个器官,导致全身炎症和随后大脑中的神经元功能障碍,从而导致 POCD。然后讨论了研究方向,包括在更多的临床 POCD 动物模型和临床试验中分析炎性小体、研究参与 POCD 的炎性小体类型,以及调查炎性小体是否发生在手术部位、循环血液和外周器官中。最后,我们讨论了使用新技术和方法研究 POCD 中炎性小体的潜在益处。对 POCD 中炎性小体的深入研究可能会对临床实践产生重大影响。