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.

中文翻译：

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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由信号机制不明确引发的常见并发症。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 （EV） 组成、潜在的外周到大脑信使的影响，以及它们与神经认知结果的关联。方法 我们在术前和术后时间点 （4 、 8 、 24 和 48 小时） 绘制了 12 例患者 （6 例神经认知结果良好，6 例神经认知结果差） 的血浆衍生 EVs 的 microRNA组和蛋白质组。在血浆和脑脊液 （CSF） 来源的 EVs 中通过流式细胞术证实补体 C3-EV 关联，使用酶联免疫吸附测定法测定血浆总和 CSF C3 和 C3a 浓度。结果 差异表达分析发现 8 个失调的 EV microRNAs （miRNAs） 仅在神经认知结局较差组中。通路分析表明 EV 靶组织中增殖途径的潜在下调以及细胞外基质和炎症反应通路的激活。蛋白质组分析显示免疫相关 EV 蛋白（包括补体系统蛋白）的时间依赖性增加，尤其是 EV 表面相关 C3。这种向上的动力学在较差的神经认知结局组中较早地检测到。有趣的是，来自同一组的 CSF 衍生的 EVs 在 48 小时时显示 C3 急剧下降，而良好的神经认知结果组中的浓度保持不变。在功能上，补体系统在血浆中两个患者组中均被激活，但仅在 CSF 中神经认知结局不佳组中被激活。 结论 我们的研究结果强调了手术对血浆和 CSF 衍生的 EVs 的影响，特别是在神经认知结果不佳的患者中，表明 EVs 的潜在作用。样本量小，需要用更大的患者群体进行验证。