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人脑细胞外液（extracellular fluids, ECF）展开检测，以评估与缺血性脑损伤相关的蛋白质水平变化。研究采用基于等压标记与质谱法的鸟枪法蛋白质组学方法，对6例缺血性脑卒中患者梗死核心（infarct core, IC）、半暗带（penumbra, P）以及未受影响的对侧（contralateral, CT）脑区的微透析液（microdialysates, MDs）进行对比分析。定量分析结果显示，相较于对侧脑区样本，梗死核心或半暗带区域共有53种蛋白质的表达量显著升高。研究进一步采用酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA），对14例无关对照者与14例脑卒中患者的血液样本，开展了谷胱甘肽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）的检测。结果显示，上述三种蛋白的表达量分别上调了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。本研究证实了细胞外液可作为高效的样本来源，为后续挖掘脑卒中血液标志物提供了重要支撑。