Braun David J, Hatton Kevin W, Fraser Justin F, Flight Robert M, Moseley Hunter N B, Bailey Caleb S, Morganti Josh M, Zhang Bingqing, Ariyapala Ishara S, Kim Tae K, Van Eldik Linda J
Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA; Department of Neuroscience, University of Kentucky, Lexington, KY 40536, USA.
Department of Anesthesiology, University of Kentucky, Lexington, KY 40536, USA.
J Stroke Cerebrovasc Dis. 2025 Jun;34(6):108304. doi: 10.1016/j.jstrokecerebrovasdis.2025.108304. Epub 2025 Apr 1.
Aneurysmal subarachnoid hemorrhage (aSAH) is a relatively uncommon but high mortality form of stroke that can result in long-lasting disability. A better understanding of key neuroinflammatory changes during the early phase (<72 h) may provide potential avenues of treatment.
In an attempt to understand these early changes, we recruited 7 aSAH patients for profiling of longitudinal plasma and cerebrospinal fluid (CSF) proteins at up to 72 h post injury. We additionally compared this to control plasma obtained previously from healthy elderly volunteers. Using the Alamar Biosciences NULISAseq platform, we obtained a comprehensive picture of early peripheral and central inflammatory changes after injury.
This study demonstrated very early plasma changes across 107 inflammatory proteins, 22 of which showed significant correlations between plasma and CSF. Of these, CXCL12, IL-15, and SAA1 are detectably elevated <24 h in plasma, significantly correlated with CSF levels, and altered as a function of aSAH progression over time during this early phase.
This study demonstrates the feasibility of measuring a large number of inflammatory proteins in CSF and plasma from aSAH patients soon after injury. Despite the small sample size and limitations of the control group, we identified several previously reported "hits" that may offer prognostic utility and/or therapeutic potential for aSAH patients: CXCL12, IL-15, and SAA1.
动脉瘤性蛛网膜下腔出血(aSAH)是一种相对罕见但死亡率高的中风形式,可导致长期残疾。更好地了解早期阶段(<72小时)关键的神经炎症变化可能提供潜在的治疗途径。
为了了解这些早期变化,我们招募了7名aSAH患者,在受伤后长达72小时对其血浆和脑脊液(CSF)蛋白进行纵向分析。我们还将此与先前从健康老年志愿者获得的对照血浆进行比较。使用阿拉玛生物科学公司的NULISAseq平台,我们获得了受伤后早期外周和中枢炎症变化的全面情况。
本研究显示了107种炎症蛋白在血浆中的非常早期的变化,其中22种在血浆和脑脊液之间显示出显著相关性。其中,CXCL12、IL-15和SAA1在血浆中<24小时可检测到升高,与脑脊液水平显著相关,并在这个早期阶段随aSAH进展而随时间变化。
本研究证明了在aSAH患者受伤后不久测量脑脊液和血浆中大量炎症蛋白的可行性。尽管样本量小且对照组存在局限性,但我们确定了几个先前报道的“靶点”,它们可能为aSAH患者提供预后效用和/或治疗潜力:CXCL12、IL-15和SAA1。