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）开展探究，旨在评估与缺血性损伤相关的蛋白质水平变化。研究采集了6名缺血性脑卒中患者梗死核心区（infarct core, IC）、缺血半暗带（penumbra, P）以及未受累对侧脑区（unaffected contralateral, CT）的微透析液（microdialysates, MDs），并采用基于等压标记与质谱技术的鸟枪法蛋白质组学方法进行对比分析。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测定（enzyme-linked immunosorbent assay, ELISA），对14名无关对照者与14名脑卒中患者的血液样本中的谷胱甘肽S-转移酶P（glutathione S-transferase P, GSTP1）、过氧化物还原酶1（peroxiredoxin-1, PRDX1）以及S100B蛋白（protein S100-B, S100B）进行了检测；结果显示三者的表达量分别较对照升高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。本研究证实了脑细胞外液作为高效样本来源的价值，可为后续脑卒中血液标志物的发掘提供重要依据。