Hasselblatt Martin, Jeibmann Astrid, Riesmeier Barbara, Maintz David, Schäbitz Wolf-Rüdiger
Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48129, Münster, Germany.
Acta Neuropathol. 2007 Jan;113(1):45-51. doi: 10.1007/s00401-006-0152-y. Epub 2006 Oct 18.
Granulocyte-colony stimulating factor (G-CSF) receptor signaling counteracts detrimental pathways in ischemic stroke. In rodents, neuroprotection provided by the G-CSF system involves up-regulation of the G-CSF receptor and its ligand, G-CSF, during cerebral ischemia. The confirmation of a similar response in the human brain would be an important rationale for the use of G-CSF in clinical stroke trials. Therefore, the temporal and cellular profile of G-CSF and G-CSF receptor expression was examined in a series of human stroke brains. The median age of the 21 stroke patients was 67 years; median time from death to autopsy was 24 h (range: 10-67 h). In acute ischemic stroke, strong neuronal G-CSF receptor immunoreactivity was encountered in the infarct area and the peri-infarct rim as compared to the contralateral cortex. In subacute infarctions, microglial and macrophage G-CSF receptor immunoreactivity predominated, whereas chronic infarction was characterized by the presence of G-CSF receptor expressing reactive astrocytes. Neuronal G-CSF expression was encountered very early upon ischemic stroke. At later time-points, an up-regulation of vascular G-CSF expression in the peri-infarct area prevailed. In conclusion, the observed up-regulation of G-CSF receptors and G-CSF points towards a role in the pathophysiology of human ischemic stroke.
粒细胞集落刺激因子（G-CSF）受体信号传导可抵消缺血性卒中的有害途径。在啮齿动物中，G-CSF系统提供的神经保护作用涉及脑缺血期间G-CSF受体及其配体G-CSF的上调。证实人类大脑中存在类似反应将是在临床卒中试验中使用G-CSF的重要理论依据。因此，在一系列人类卒中大脑中检测了G-CSF和G-CSF受体表达的时间和细胞特征。21例卒中患者的中位年龄为67岁；从死亡到尸检的中位时间为24小时（范围：10-67小时）。在急性缺血性卒中中，与对侧皮质相比，在梗死区域和梗死周边可见强烈的神经元G-CSF受体免疫反应性。在亚急性梗死中，小胶质细胞和巨噬细胞的G-CSF受体免疫反应性占主导，而慢性梗死的特征是存在表达G-CSF受体的反应性星形胶质细胞。缺血性卒中后很早就可检测到神经元G-CSF表达。在后期，梗死周边区域的血管G-CSF表达上调占主导。总之，观察到的G-CSF受体和G-CSF上调表明其在人类缺血性卒中病理生理学中发挥作用。
