Nyquist Paul A, Wang Honghui, Suffredini Anthony F
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Acta Neurochir Suppl. 2013;115:23-5. doi: 10.1007/978-3-7091-1192-5_6.
Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease. It has many sequelae, including vasospasm and delayed ischemic neurological deficits (DINDs). We explored the blood proteome in patients with aSAH using transcranial Doppler (TCD) velocity as a guide to patients who are at risk for symptomatic vasospasm and DIND. Blood was drawn on all days that patients were observed in the neurocritical care unit (NCCU) after aSAH. A team of neurologists and neurosurgeons identified patients with clinical evidence of vasospasm and DIND. Serum was fractionated using protein chips and surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS). We detected a pattern of protein expression associated with those at risk for elevated TCD velocities by day 8, compared with blood collected in the presymptomatic stage (days 1-3). We further analyzed serum using pooled samples from study entry to the time of elevated TCD velocities using a protein microarray that analyzed 500 human proteins thematically oriented toward inflammation. After identifying several candidates with elevated concentrations in the pooled samples, we then used reverse protein arrays to quantitate the concentration of potential candidate proteins in the individual samples. Proteins with significantly elevated concentrations included apolipoprotein-E, apolipoprotein-A, serum amyloid protein-4, and serum amyloid protein-P. Future studies in larger sample populations are needed to evaluate these biomarkers further as representative of biosystems involved in vasospasm and DIND or as potential biomarkers predictive of risk associated with disease.
动脉瘤性蛛网膜下腔出血（aSAH）是一种毁灭性的神经系统疾病。它有许多后遗症，包括血管痉挛和迟发性缺血性神经功能缺损（DINDs）。我们以经颅多普勒（TCD）速度为指导，探索了aSAH患者的血液蛋白质组，以确定有症状性血管痉挛和DIND风险的患者。在aSAH后患者在神经重症监护病房（NCCU）接受观察的所有日子里均采集血液。一组神经科医生和神经外科医生确定了有血管痉挛和DIND临床证据的患者。使用蛋白质芯片和表面增强激光解吸电离飞行时间质谱（SELDI-TOF MS）对血清进行分级分离。与症状前期（第1 - 3天）采集的血液相比，我们检测到了与第8天TCD速度升高风险相关的蛋白质表达模式。我们使用分析500种以炎症为主题的人类蛋白质的蛋白质微阵列，对从研究入组到TCD速度升高时的合并样本进行进一步血清分析。在确定合并样本中几种浓度升高的候选蛋白后，我们随后使用反向蛋白质阵列对各个样本中潜在候选蛋白的浓度进行定量。浓度显著升高的蛋白质包括载脂蛋白 - E、载脂蛋白 - A、血清淀粉样蛋白 - 4和血清淀粉样蛋白 - P。需要在更大样本量人群中进行进一步研究，以进一步评估这些生物标志物，作为涉及血管痉挛和DIND的生物系统的代表，或作为预测疾病相关风险的潜在生物标志物。
