Granulocyte colony-stimulating factor enhances anglogenesis after focal cerebral ischemia
Granulocyte colony-stimulating factor enhances anglogenesis after focal cerebral ischemia
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DOI：
10.1016/j.brainres.2005.07.076
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发表时间：
2005-10-05
期刊：
影响因子：
2.9
通讯作者：
Roh, JK
中科院分区：
文献类型：
--
作者：
Lee, ST;Chu, K;Roh, JK
粒细胞集落刺激因子 (G-CSF) 是一种神经保护剂，可激活内皮增殖和骨髓干细胞动员。我们研究了 G-CSF 对局灶性脑缺血后血管生成和神经功能恢复的影响。在大鼠中诱导短暂性局部缺血后，给予G-CSF（50μg/kg/天，腹腔注射）或PBS 3天。我们评估了功能恢复、梗塞体积、炎症浸润、血脑屏障 (131313) 破坏、半球萎缩、内皮一氧化氮合酶 (eNOS) 和血管生成素的蛋白表达以及 G-CSF 给药的治疗时间窗。然后我们分析了内皮细胞增殖、血管表面积、分支点数量和血管长度。 G-CSF治疗改善了行为恢复并减少了梗塞体积、炎症浸润、131313破坏和半球萎缩。缺血后2小时、第1天或第4天开始注射G-CSF，与第7天开始注射相比，功能恢复更好，半球萎缩程度更大。与仅缺血组相比，G-CSF组的血管表面积、血管分支点、血管长度、BrdU(+)内皮细胞数量和eNOS/血管生成素-2表达显着增加。与第7天开始注射相比，第1天开始注射G-CSF诱导了更大的内皮增殖。在这项研究中，我们提供的证据表明，G-CSF 可增强血管生成并减少缺血性损伤，从而促进长期功能恢复。 (c) 2005 Elsevier B.V. 保留所有权利。
Granulocyte colony-stimulating factor (G-CSF) is a neuroprotective agent and activates endothelial proliferation and bone marrow stem cell mobilization. We studied the effect of G-CSF on angiogenesis and neurological recovery after focal cerebral ischemia. After the induction of transient focal ischemia in rats, G-CSF (50 mu g/kg/day, i.p.) or PBS was administered for 3 days. We evaluated the functional recovery, infarct volume, inflammatory infiltration, blood-brain barrier (131313) disruption, hemispheric atrophy, protein expressions of endothelial nitric oxide synthase (eNOS) and angiopoietins, and the therapeutic time window of G-CSF administration. We then analyzed enclothelial cell proliferation, the vascular surface area, the number of branch points, and the vascular length. G-CSF treatment improved behavioral recovery and reduced the infarct volume, the inflammatory infiltration, the 131313 disruption, and the hemispheric atrophy. G-CSF injection, starting at 2 h, I day, or 4 days after ischemia, resulted in a better functional recovery and a greater reduction in hemispheric atrophy than injection starting at day 7. The vascular surface area, the vascular branch points, the vascular length, the number of BrdU(+) endothelial cells, and eNOS/ angiopoietin-2 expression were significantly increased in the G-CSF group compared with the ischemia-only group. G-CSF injection starting at I day induced larger endothelial proliferation compared with injection starting at 7 days. In this study, we provide evidences that G-CSF enhances the angiogenesis and reduces the ischemic damage, which promotes the long-term functional recovery. (c) 2005 Elsevier B.V. All rights reserved.