Granulocyte Colony-Stimulating Factor Enhances Arteriogenesis and Ameliorates Cerebral Damage in a Mouse Model of Ischemic Stroke
Granulocyte Colony-Stimulating Factor Enhances Arteriogenesis and Ameliorates Cerebral Damage in a Mouse Model of Ischemic Stroke
复制标题
DOI：
10.1161/strokeaha.110.597799
复制
发表时间：
2011-03-01
期刊：
影响因子：
8.3
通讯作者：
Kitagawa, Kazuo
中科院分区：
文献类型：
--
作者：
Sugiyama, Yukio;Yagita, Yoshiki;Kitagawa, Kazuo
背景和目的-促进侧支动脉生长是治疗闭塞动脉引起的心血管缺血性疾病的有效治疗方法。粒细胞-巨噬细胞集落刺激因子（GM-CSF）因其通过单核细胞上调机制促进动脉生成、改善脑损伤的能力而受到关注。然而，最近的临床研究测试其在心肌缺血中的疗效提出了关于其安全性的问题。我们测试了替代集落刺激因子对侧支动脉生长和脑protection. Methods的影响，脑低灌注通过闭塞C57/BL 6小鼠的左颈总动脉。手术后，每天给予粒细胞集落刺激因子、巨噬细胞集落刺激因子或GM-CSF（100 μ g/kg/天），持续5天。在集落刺激因子治疗后，可观察到软脑膜炎的血管构筑和Willis环。循环血单核细胞和Mac-2阳性细胞在脑背表面进行了测定。一组动物进行了随后的同侧大脑中动脉闭塞和梗死体积assessed.Results-Granulocyte集落刺激因子以及GM-CSF促进软脑膜侧支生长后，颈总动脉闭塞。粒细胞集落刺激因子和GM-CSF增加循环血单核细胞和Mac-2阳性细胞在背侧脑表面，这表明单核细胞上调耦合的机制可能是共享的。粒细胞集落刺激因子可减少大脑中动脉闭塞后的脑血容量，与GM-CSF相似。巨噬细胞集落刺激因子显示没有these effects. Conclusions-粒细胞集落刺激因子增强侧支动脉生长，减少脑缺血小鼠模型中的梗死体积，类似于GM-CSF。（中风。2011;42：770-775）。
Background and Purpose-Enhancing collateral artery growth is a potent therapeutic approach to treat cardiovascular ischemic disease from occlusive artery. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has gained attention for its ability to promote arteriogenesis, ameliorating brain damage, by the mechanisms involving monocyte upregulation. However, the recent clinical study testing its efficacy in myocardial ischemia has raised the question about its safety. We tested alternative colony-stimulating factors for their effects on collateral artery growth and brain protection.Methods-Brain hypoperfusion was produced by occluding the left common carotid artery in C57/BL6 mice. After the surgery, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, or GM-CSF (100 mu g/kg/day) was administered daily for 5 days. The angioarchitecture for leptomeningeal anastomoses and the circle of Willis were visualized after the colony-stimulating factor treatment. Circulating blood monocytes and Mac-2-positive cells in the dorsal surface of the brain were determined. A set of animals underwent subsequent ipsilateral middle cerebral artery occlusion and infarct volume was assessed.Results-Granulocyte colony-stimulating factor as well as GM-CSF promoted leptomeningeal collateral growth after common carotid artery occlusion. Both granulocyte colony-stimulating factor and GM-CSF increased circulating blood monocytes and Mac-2-positive cells in the dorsal brain surface, suggesting the mechanisms coupled to monocyte upregulation might be shared. Infarct volume after middle cerebral artery occlusion was reduced by granulocyte colony-stimulating factor, similarly to GM-CSF. Macrophage colony-stimulating factor showed none of theses effects.Conclusions-Granulocyte colony-stimulating factor enhances collateral artery growth and reduces infarct volume in a mouse model of brain ischemia, similarly to GM-CSF. (Stroke. 2011;42:770-775.)