Yang Bosco Seong Kyu, O'Keefe Lena, Hinds Sarah, Chen Hua, Paz Athziry, Savarraj Jude, Jeong Han-Gil, Han Moon-Ku, Gusdon Aaron, Ren Xuefang Sophie, Blackburn Spiros, Choi Huimahn Alex
Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Novel treatments for Acute Brain Injury (NABI) Institution, UT Health Houston, Houston, TX, USA.
J Cereb Blood Flow Metab. 2025 Aug 20:271678X251361250. doi: 10.1177/0271678X251361250.
Cerebral edema (CE) is a major component of early brain injury from aneurysmal subarachnoid hemorrhage (SAH). Despite the utility of blood-based protein markers, biomarkers targeting cerebral edema have yet to be developed. We performed a targeted proteomic search analyzing 141 proteins in plasma samples taken from 80 adult patients within 48 hours after aneurysmal rupture to identify plasma biomarkers of cerebral edema. The protein expression profiles were analyzed for associations with a higher level of the subarachnoid hemorrhage early brain edema score measured in admission computed tomography scans. Five differentially expressed proteins-brorin, ectodysplasin A2 receptor, layilin, scavenger receptor class A member 5, and activin A receptor like type 1 (ACVRL1)-were identified. To confirm our findings, in a separate cohort of 75 adult patients with SAH, these biomarker candidates was analyzed using a different confirmatory analytic method-enzyme-linked immunosorbent assay-based on the plasma samples collected within 48 hours after aneurysmal rupture. ACVRL1 levels consistently showed a decrease expression levels as the severity of edema increased. The association between CE and ACVRL1 was significant before and after adjusting for patient factors.
脑水肿（CE）是动脉瘤性蛛网膜下腔出血（SAH）所致早期脑损伤的主要组成部分。尽管基于血液的蛋白质标志物具有实用价值，但针对脑水肿的生物标志物尚未开发出来。我们进行了一项靶向蛋白质组学研究，分析了80例成年患者在动脉瘤破裂后48小时内采集的血浆样本中的141种蛋白质，以确定脑水肿的血浆生物标志物。分析蛋白质表达谱与入院计算机断层扫描中测量的蛛网膜下腔出血早期脑水肿评分较高水平之间的关联。鉴定出五种差异表达的蛋白质——溴蛋白、外胚层发育不良蛋白A2受体、层粘连蛋白、A类清道夫受体成员5和激活素A受体样1型（ACVRL1）。为了证实我们的发现，在另一组75例成年SAH患者中，基于动脉瘤破裂后48小时内采集的血浆样本，使用不同的验证分析方法——酶联免疫吸附测定法，对这些生物标志物候选物进行了分析。随着水肿严重程度的增加，ACVRL1水平持续显示出表达水平降低。在调整患者因素前后，CE与ACVRL1之间的关联均具有显著性。
