Changes in circulating extracellular vesicle cargo are associated with cognitive decline after major surgery: an observational case-control study.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

British journal of anaesthesia Pub Date : 2024-10-18 DOI:10.1016/j.bja.2024.07.040

Souren Mkrtchian,Maria Eldh,Anette Ebberyd,Susanne Gabrielsson,Ákos Végvári,Sven-Erik Ricksten,Mattias Danielson,Jonatan Oras,Andreas Wiklund,Lars I Eriksson,Marta Gómez-Galán

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Abstract

BACKGROUND Postoperative neurocognitive decline is a frequent complication triggered by unclear signalling mechanisms. This observational case-control study investigated the effects of hip or knee replacement surgery on the composition of circulating extracellular vesicles (EVs), potential periphery-to-brain messengers, and their association with neurocognitive outcomes. METHODS We mapped the microRNAome and proteome of plasma-derived EVs from 12 patients (six with good and six with poor neurocognitive outcomes at 3 months after surgery) at preoperative and postoperative timepoints (4, 8, 24, and 48 h). Complement C3-EV association was confirmed by flow cytometry in plasma- and cerebrospinal fluid (CSF)-derived EVs, with total plasma and CSF C3 and C3a concentrations determined using enzyme-linked immunosorbent assay. RESULTS Differential expression analysis found eight dysregulated EV microRNAs (miRNAs) exclusively in the poor neurocognitive outcomes group. Pathway analysis suggested potential downregulation of proliferative pathways and activation of extracellular matrix and inflammatory response pathways in EV target tissues. Proteome analysis revealed a time-dependent increase in immune-related EV proteins, including complement system proteins, notably EV surface-associated C3. Such upward kinetics was detected earlier in the poor neurocognitive outcomes group. Interestingly, CSF-derived EVs from the same group showed a drastic drop of C3 at 48 h with unchanged concentrations in the good neurocognitive outcomes group. Functionally, the complement system was activated in both patient groups in plasma, but only in the poor neurocognitive outcomes group in CSF. CONCLUSIONS Our findings highlight the impact of surgery on plasma- and CSF-derived EVs, particularly in patients with poor neurocognitive outcomes, indicating a potential role for EVs. The small sample size necessitates verification with a larger patient cohort.

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循环细胞外囊泡货物的变化与大手术后认知能力下降有关：一项观察性病例对照研究。

背景术后神经认知能力下降是一种常见的并发症，其诱因是信号机制不明确。这项观察性病例对照研究调查了髋关节或膝关节置换手术对循环细胞外囊泡（EVs）组成的影响（EVs是潜在的外周到大脑信使）及其与神经认知结果的关系。方法：我们绘制了 12 例患者（6 例神经认知结果良好，6 例神经认知结果较差，术后 3 个月）在术前和术后时间点（4、8、24 和 48 小时）的血浆衍生 EVs 的 microRNA 组和蛋白质组。血浆和脑脊液（CSF）衍生 EV 的流式细胞术证实了补体 C3-EV 的关联，血浆和 CSF C3 和 C3a 的总浓度采用酶联免疫吸附测定法测定。通路分析表明，EV靶组织中的增殖通路可能被下调，细胞外基质和炎症反应通路可能被激活。蛋白质组分析显示，与免疫相关的EV蛋白随时间增加，包括补体系统蛋白，尤其是EV表面相关的C3。这种上升动力学在神经认知结果不良组中更早被发现。有趣的是，同一组的 CSF 衍生 EV 在 48 小时后显示出 C3 的急剧下降，而神经认知结果良好组的 C3 浓度保持不变。结论我们的研究结果突显了手术对血浆和 CSF 衍生 EVs 的影响，尤其是对神经认知结果不佳的患者，这表明 EVs 具有潜在的作用。由于样本量较小，有必要在更大的患者群中进行验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of anaesthesia 医学-麻醉学

CiteScore

13.50

自引率

7.10%

发文量

488

审稿时长

27 days

期刊介绍： The British Journal of Anaesthesia (BJA) is a prestigious publication that covers a wide range of topics in anaesthesia, critical care medicine, pain medicine, and perioperative medicine. It aims to disseminate high-impact original research, spanning fundamental, translational, and clinical sciences, as well as clinical practice, technology, education, and training. Additionally, the journal features review articles, notable case reports, correspondence, and special articles that appeal to a broader audience. The BJA is proudly associated with The Royal College of Anaesthetists, The College of Anaesthesiologists of Ireland, and The Hong Kong College of Anaesthesiologists. This partnership provides members of these esteemed institutions with access to not only the BJA but also its sister publication, BJA Education. It is essential to note that both journals maintain their editorial independence. Overall, the BJA offers a diverse and comprehensive platform for anaesthetists, critical care physicians, pain specialists, and perioperative medicine practitioners to contribute and stay updated with the latest advancements in their respective fields.