Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
J Cereb Blood Flow Metab. 2021 Oct;41(10):2524-2533. doi: 10.1177/0271678X211012110. Epub 2021 May 5.
Lipocalin-2 mediates neuro-inflammation and iron homeostasis in vascular injuries of the central nervous system (CNS) and is upregulated in extra-CNS systemic inflammation. We postulate that cerebrospinal fluid (CSF) and blood lipocalin-2 levels are associated with markers of inflammation and functional outcome in subarachnoid hemorrhage (SAH). We prospectively enrolled 67 SAH subjects, serially measured CSF and plasma lipocalin-2, matrix metallopeptidase 9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on post-SAH days 1-5 and assessed outcome by modified Rankin Scale (mRS) every 3 months. Unfavorable outcome is defined as mRS > 2. Twenty non-SAH patients undergoing lumbar drain trial were enrolled as controls. Lipocalin-2 was detectable in the CSF and significantly higher in SAH compared to controls (p < 0.0001). Higher CSF LCN2 throughout post-SAH days 1-5 was associated with unfavorable outcome at 3 (p = 0.0031) and 6 months (p = 0.014). Specifically, higher CSF lipocalin-2 on post-SAH days 3 (p = 0.036) and 5 (p = 0.016) were associated with unfavorable 3-month outcome. CSF lipocalin-2 levels positively correlated with CSF IL-6, TNF-α and MMP-9 levels. Higher plasma lipocalin-2 levels over time were associated with worse 6-month outcome. Additional studies are required to understand the role of lipocalin-2 in SAH and to validate CSF lipocalin-2 as a potential biomarker for SAH outcome.
载脂蛋白 2 介导中枢神经系统（CNS）血管损伤中的神经炎症和铁稳态，并且在外周 CNS 全身炎症中上调。我们假设脑脊髓液（CSF）和血液载脂蛋白 2 水平与蛛网膜下腔出血（SAH）中的炎症标志物和功能结果相关。我们前瞻性纳入 67 例 SAH 患者，在 SAH 后第 1-5 天连续测量 CSF 和血浆载脂蛋白 2、基质金属蛋白酶 9（MMP-9）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α），并每隔 3 个月通过改良 Rankin 量表（mRS）评估预后。不良预后定义为 mRS>2。20 例接受腰椎引流试验的非 SAH 患者作为对照。CSF 中可检测到载脂蛋白 2，且 SAH 患者明显高于对照组（p<0.0001）。SAH 后第 1-5 天 CSF 中较高的 LCN2 与 3 个月（p=0.0031）和 6 个月（p=0.014）时的不良预后相关。具体而言，SAH 后第 3 天（p=0.036）和第 5 天（p=0.016）较高的 CSF 载脂蛋白 2 与 3 个月时的不良预后相关。CSF 载脂蛋白 2 水平与 CSF IL-6、TNF-α和 MMP-9 水平呈正相关。随着时间的推移，较高的血浆载脂蛋白 2 水平与 6 个月时的不良预后相关。需要进一步研究以了解载脂蛋白 2 在 SAH 中的作用，并验证 CSF 载脂蛋白 2 是否作为 SAH 预后的潜在生物标志物。
