Department of Neurosciences, Neurosurgery, Uppsala University, Uppsala, Sweden.
PLoS One. 2022 Mar 24;17(3):e0263460. doi: 10.1371/journal.pone.0263460. eCollection 2022.
The complexity of the inflammatory response post subarachnoid hemorrhage (SAH) may require temporal analysis of multiple protein biomarkers simultaneously to be more accurately described.
Ventricular cerebrospinal fluid was collected at days 1, 4 and 10 after SAH in 29 patients. Levels of 92 inflammation-related proteins were simultaneously measured using Target 96 Inflammation ® assay (Olink Proteomics, Uppsala, Sweden) based on Proximity Extension Assay (PEA) technology. Twenty-eight proteins were excluded from further analysis due to lack of >50% of measurable values. Temporal patterns of the remaining 64 proteins were analyzed. Repeated measures ANOVA and its nonparametric equivalent Friedman's ANOVA were used for comparisons of means between time points.
Four different patterns (Groups A-D) were visually observed with an early peak and gradually decreasing trend (11 proteins), a middle peak (10 proteins), a late peak after a gradually increasing trend (30 proteins) and no specific pattern (13 proteins). Statistically significant early peaks defined as Day 1 > Day 4 values were noticed in 4 proteins; no significant decreasing trends defined as Day 1 > Day 4 > Day 10 values were observed. Two proteins showed significant middle peaks (i.e. Day 1 < Day 4 > Day 10 values). Statistically significant late peaks (i.e. Day 4 < Day 10 values) and increasing trends (i.e. Day 1 < Day 4 < Day 10 values) were observed in 14 and 10 proteins, respectively. Four of Group D proteins showed biphasic peaks and the rest showed stable levels during the observation period.
The comprehensive data set provided in this explorative study may act as an illustration of an inflammatory profile of the acute phase of SAH showing groups of potential protein biomarkers with similar temporal patterns of activation, thus facilitating further research on their role in the pathophysiology of the disease.
蛛网膜下腔出血（SAH）后炎症反应的复杂性可能需要同时分析多个蛋白质生物标志物，以更准确地描述。
在 29 名患者中，在 SAH 后第 1、4 和 10 天收集脑室脑脊液。使用基于邻近延伸分析（PEA）技术的靶向 96 炎症 ® 分析（Olink Proteomics，Uppsala，瑞典）同时测量 92 种炎症相关蛋白的水平。由于缺乏 >50%的可测量值，28 种蛋白质被排除在进一步分析之外。分析其余 64 种蛋白质的时间模式。使用重复测量方差分析及其非参数等效 Friedman 的方差分析比较各时间点的平均值。
观察到 4 种不同的模式（A-D 组），具有早期峰值和逐渐下降趋势（11 种蛋白质）、中期峰值（10 种蛋白质）、逐渐增加趋势后的晚期峰值（30 种蛋白质）和无特定模式（13 种蛋白质）。注意到 4 种蛋白质出现明显的早期峰值（即第 1 天>第 4 天）；未观察到显著的下降趋势（即第 1 天>第 4 天>第 10 天）。两种蛋白质显示出明显的中期峰值（即第 1 天<第 4 天>第 10 天）。观察到 14 种蛋白质具有统计学显著的晚期峰值（即第 4 天<第 10 天）和增加趋势（即第 1 天<第 4 天<第 10 天），10 种蛋白质显示出相似的趋势。D 组的 4 种蛋白质显示出双峰峰值，其余蛋白质在观察期间显示出稳定水平。
本探索性研究提供的综合数据集可以作为蛛网膜下腔出血急性期炎症特征的说明，显示出具有相似激活时间模式的潜在蛋白质生物标志物组，从而促进对其在疾病病理生理学中作用的进一步研究。
