Brain Extracellular Fluid Protein Changes in Acute Stroke Patients

In vivo human brain extracellular fluids (ECF) of acute stroke patients were investigated to assess the changes in protein levels associated with ischemic damages. Microdialysates (MDs) from the infarct core (IC), the penumbra (P), and the unaffected contralateral (CT) brain regions of patients suffering an ischemic stroke (n = 6) were compared using a shotgun proteomic approach based on isobaric tagging and mass spectrometry. Quantitative analysis showed 53 proteins with increased amounts in the IC or P with respect to the CT samples. Glutathione S-transferase P (GSTP1), peroxiredoxin-1 (PRDX1), and protein S100-B (S100B) were further assessed with ELISA on the blood of unrelated control (n = 14) and stroke (n = 14) patients. Significant increases of 8- (p = 0.0002), 20- (p = 0.0001), and 11-fold (p = 0.0093) were found, respectively. This study highlights the value of ECF as an efficient source to further discover blood stroke markers.

本研究针对急性脑卒中患者的在体人脑细胞外液（extracellular fluids, ECF）展开探究，旨在评估与缺血性脑损伤相关的蛋白质水平变化。本研究纳入6例缺血性脑卒中患者，采集其梗死核心区（infarct core, IC）、半暗带（penumbra, P）以及未受累对侧脑区（unaffected contralateral, CT）的微透析液（Microdialysates, MDs），并采用基于同量异位素标记与质谱技术的鸟枪法蛋白质组学方法开展对比分析。定量分析结果显示，相较于CT样本，IC或P区域内共有53种蛋白质的表达量显著上调。研究进一步采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA），对14例无关对照个体与14例脑卒中患者的血液样本中谷胱甘肽S-转移酶P（Glutathione S-transferase P, GSTP1）、过氧化物还原蛋白-1（peroxiredoxin-1, PRDX1）以及S100B蛋白（protein S100-B, S100B）的水平进行检测。检测结果显示，三者的表达量分别上调8倍（p=0.0002）、20倍（p=0.0001）与11倍（p=0.0093），差异均具有统计学意义。本研究证实了人脑细胞外液（ECF）作为高效生物样本来源的价值，可为后续脑卒中血液标志物的发掘提供重要参考。