Granulocyte colony‐stimulating factor has a negative effect on stroke outcome in a murine model

Granulocyte colony‐stimulating factor has a negative effect on stroke outcome in a murine model
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DOI:
10.1111/j.1460-9568.2007.05640.x
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发表时间:
2007-07
影响因子:
3.4
通讯作者:
A. Taguchi;Zhongmin Wen;K. Myojin;T. Yoshihara;T. Nakagomi;Daisuke Nakayama;Hidekazu Tanaka;T. So
A. Taguchi;Zhongmin Wen;K. Myojin;T. Yoshihara;T. Nakagomi;Daisuke Nakayama;Hidekazu Tanaka;T. So
中科院分区:
医学3区
文献类型:
--
作者:
A. Taguchi;Zhongmin Wen;K. Myojin;T. Yoshihara;T. Nakagomi;Daisuke Nakayama;Hidekazu Tanaka;T. So

文献摘要

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中风后给予CD 34阳性细胞已被证明通过加速啮齿动物模型中的血管生成和神经发生对功能恢复具有有益作用。已知粒细胞集落刺激因子(G-CSF)可动员骨髓中的CD 34阳性细胞,并在短暂性缺血应激后显示出神经保护特性。这使我们研究了G-CSF给药对小鼠中风后的影响。我们利用永久性结扎左侧大脑中动脉的M1远端部分,在CB-17小鼠中建立可重现的局灶性脑缺血模型。与对照组相比,G-CSF处理的动物显示皮质萎缩和行为功能受损。基于CD 11b阳性和F4/80阳性细胞浸润脑梗死区域,G-CSF对结局的负面影响与G-CSF诱导过度炎症反应相关。虽然已经开始了G-CSF治疗心肌和肢体缺血的临床试验,但我们的结果表明,将这些结果应用于脑缺血时应谨慎。
The administration of CD34‐positive cells after stroke has been shown to have a beneficial effect on functional recovery by accelerating angiogenesis and neurogenesis in rodent models. Granulocyte colony‐stimulating factor (G‐CSF) is known to mobilize CD34‐positive cells from bone marrow and has displayed neuroprotective properties after transient ischemic stress. This led us to investigate the effects of G‐CSF administration after stroke in mouse. We utilized permanent ligation of the M1 distal portion of the left middle cerebral artery to develop a reproducible focal cerebral ischemia model in CB‐17 mice. Animals treated with G‐CSF displayed cortical atrophy and impaired behavioral function compared with controls. The negative effect of G‐CSF on outcome was associated with G‐CSF induction of an exaggerated inflammatory response, based on infiltration of the peri‐infarction area with CD11b‐positive and F4/80‐positive cells. Although clinical trials with G‐CSF have been started for the treatment of myocardial and limb ischemia, our results indicate that caution should be exercised in applying these results to cerebral ischemia.