Circulating Damage Marker Profiles Support a Neuroprotective Effect of Erythropoietin in Ischemic Stroke Patients
Circulating Damage Marker Profiles Support a Neuroprotective Effect of Erythropoietin in Ischemic Stroke Patients
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DOI：
10.2119/molmed.2011.00259
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发表时间：
2011-11-01
影响因子：
5.7
通讯作者：
Herrmann, Manfred
中科院分区：
文献类型：
--
作者：
Ehrenreich, Hannelore;Kaestner, Anne;Herrmann, Manfred
德国多中心EPO卒中试验正式宣布为阴性研究，该试验调查了促红细胞生成素(EPO)治疗缺血性中风的安全性和有效性。然而，探索性亚组分析显示，未接受溶栓治疗的患者在临床恢复期间最有可能受益于EPO，这一结果在哥廷根EPO卒中研究的结果中得到了证实。目前的工作调查了这一亚组患者的临床结果的积极信号是否反映了各自的卒中后生物标记物特征。德国多中心EPO卒中试验中所有不符合溶栓资格的患者都包括在内，如果他们(A)按照方案接受治疗，并且(B)至少有五个随访血样中的两个用于提取循环损伤标志物(n=163)。采用酶联免疫吸附试验检测卒中后1、2、3、4、7天血清中神经胶质标记物S100B、胶质纤维酸性蛋白(GFAP)和神经元标记物泛素C末端水解酶(UCH-L1)的含量。所有生物标志物在卒中后均增加。总体而言，EPO治疗的患者在7天的观察中有明显较低的浓度(曲线下面积)，这从所有三个标志物的综合评分(Cronbachα=0.811)和UCH-L1反映出来。S100B和GFAP表现出类似的趋势。综上所述，血清生物标记物谱作为脑损伤的结果指标，证实了促红细胞生成素在缺血性中风中的有利作用。特别是，神经元损伤标志物UCH-L1的减少可能反映了EPO的神经保护作用。(C)2011年范斯坦医学研究所，网址：http://www.molmed.org doi：10.2119/molmed.2011.00259
The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Gottingen EPO Stroke Study The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach alpha = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00259