围手术期神经认知障碍中的细胞外囊泡信号传导

摘要(中文译文)

围手术期神经认知障碍（PND），包括术后谵妄、延迟性神经认知恢复和术后神经认知障碍，是老年及脆弱手术患者的重要并发症。这些状况与住院时间延长、功能恢复受损、医疗资源利用增加以及更差的长期结局相关。现有证据表明，PND并非由单一机制驱动。相反，全身性炎症、神经血管功能障碍、血脑屏障损伤、胶质细胞激活、先天免疫信号传导以及突触损伤均被认为参与其中。然而，围手术期外周应激如何转化为持续的术后脑功能障碍，其通路仍未被完全阐明。在此背景下，细胞外囊泡（EVs）日益受到关注。作为携带蛋白质、脂质和核酸的脂质双层包裹颗粒，EVs参与细胞间及器官间通讯，并可能提供手术损伤与下游大脑反应之间的机制联系。新出现的证据提示，EV相关信号可能参与从外周炎症和血管应激向血脑屏障功能障碍、神经炎症、补体相关突触损伤及神经元功能障碍的进展过程。与此同时，EV相关货物可能为围手术期研究提供具有生物学信息价值的外周信号。本综述总结了EV信号的生物学基础、与EV研究相关的主要方法学问题，以及将EV相关信号与PND联系起来的现有临床和实验证据。本综述还讨论了来源特异性EV亚群及其与围手术期脑损伤的潜在相关性。

Abstract

Perioperative neurocognitive disorders (PND), including postoperative delirium, delayed neurocognitive recovery, and postoperative neurocognitive disorder, are important complications in older and vulnerable surgical patients. These conditions are associated with prolonged hospitalization, reduced functional recovery, greater healthcare utilization, and worse longer-term outcomes. Current evidence indicates that PND is not driven by a single mechanism. Instead, systemic inflammation, neurovascular dysfunction, blood-brain barrier injury, glial activation, innate immune signalling, and synaptic injury are all thought to contribute. However, the pathways by which peripheral perioperative stress is translated into sustained postoperative brain dysfunction remain incompletely understood. Extracellular vesicles (EVs) have attracted increasing attention in this context. As lipid bilayer-enclosed particles carrying proteins, lipids, and nucleic acids, EVs are involved in intercellular and inter-organ communication and may provide a mechanistic link between surgical injury and downstream cerebral responses. Emerging evidence suggests that EV-associated signals may participate in the progression from peripheral inflammation and vascular stress to blood-brain barrier dysfunction, neuroinflammation, complement-related synaptic injury, and neuronal dysfunction. In parallel, EV-associated cargo may offer a biologically informative peripheral signal for perioperative studies. This review summarizes the biological basis of EV signalling, major methodological issues relevant to EV research, and current clinical and experimental evidence linking EV-associated signals to PND. It also discusses source-specific EV populations and their potential relevance to perioperative brain injury.

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