Thomas Ajith J, Ogilvy Christopher S, Griessenauer Christoph J, Hanafy Khalid A
1Division of Neurosurgery.
2Department of Neurology, and.
J Neurosurg. 2019 Jul 1;131(1):47-53. doi: 10.3171/2018.2.JNS172828. Epub 2018 Jul 20.
Even though heme-induced cerebral inflammation contributes to many of the adverse sequelae seen in patients with subarachnoid hemorrhage (SAH), little is known about the mechanism; mouse models have shown a critical role for macrophages/microglia. Macrophage CD163 is a hemoglobin scavenger receptor involved in blood clearance after SAH. The authors hypothesized that the modified Fisher score is independently associated with cerebrospinal fluid (CSF) macrophage CD163 expression on postictal day 1, and that CSF macrophage CD163 expression is associated with 1-month neurological outcome.
CSF macrophages from 21 SAH and 28 unruptured aneurysm patients (control) were analyzed for CD163 expression using flow cytometry and confocal microscopy on postictal day 1. Significant associations with modified Fisher scale grades or modified Rankin Scale scores were determined using linear regression and a matched case control analysis.
CSF macrophage CD163 expression was significantly increased in SAH patients compared with controls (p < 0.001). The modified Fisher scale (mF) grades (β = 0.407, p = 0.005) and CSF bilirubin concentrations (β = 0.311, p = 0.015) were positively and independently associated with CSF macrophage CD163 expression when the analysis was controlled for age and sex. CSF macrophages from an SAH patient with a high mF grade had increased co-localization of CD163 and glycophorin A (CD235a, an erythrocyte marker) compared with those from an SAH patient with a low mF grade. The controls had no co-localization. CSF macrophage CD163 expression (p = 0.003) was inversely associated with 1-month neurological outcome, when SAH patients were matched based on mF grade.
This early study suggests that CSF macrophage CD163 expression, as measured by flow cytometry, may have some neuroprotective function given its inverse association with outcome and provides unique insights into the neuroinflammatory process after SAH.
尽管血红素诱导的脑部炎症导致蛛网膜下腔出血（SAH）患者出现许多不良后遗症，但其机制仍知之甚少；小鼠模型已显示巨噬细胞/小胶质细胞起关键作用。巨噬细胞CD163是一种血红蛋白清除受体，参与SAH后的血液清除。作者推测改良Fisher评分与发病后第1天脑脊液（CSF）巨噬细胞CD163表达独立相关，且CSF巨噬细胞CD163表达与1个月时的神经功能结局相关。
对21例SAH患者和28例未破裂动脉瘤患者（对照）的CSF巨噬细胞，在发病后第1天使用流式细胞术和共聚焦显微镜分析CD163表达。使用线性回归和匹配病例对照分析确定与改良Fisher量表分级或改良Rankin量表评分的显著相关性。
与对照组相比，SAH患者的CSF巨噬细胞CD163表达显著增加（p < 0.001）。在对年龄和性别进行校正后分析时，改良Fisher量表（mF）分级（β = 0.407，p = 0.005）和CSF胆红素浓度（β = 0.311，p = 0.015）与CSF巨噬细胞CD163表达呈正相关且独立相关。与mF分级低的SAH患者相比，mF分级高的SAH患者的CSF巨噬细胞中CD163与血型糖蛋白A（CD235a，一种红细胞标志物）的共定位增加。对照组无共定位。当根据mF分级对SAH患者进行匹配时，CSF巨噬细胞CD163表达（p = 0.003）与1个月时的神经功能结局呈负相关。
这项早期研究表明，通过流式细胞术测量的CSF巨噬细胞CD163表达可能具有一定的神经保护功能，因为它与结局呈负相关，并为SAH后的神经炎症过程提供了独特的见解。
