Granulocyte Colony-Stimulating Factor Enhances the Angiogenetic Effect of Indirect Bypass Surgery for Chronic Cerebral Hypoperfusion in a Rat Model
Granulocyte Colony-Stimulating Factor Enhances the Angiogenetic Effect of Indirect Bypass Surgery for Chronic Cerebral Hypoperfusion in a Rat Model
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DOI：
10.1227/neu.0b013e31820c0289
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Kuratsu, Jun-ichi
中科院分区：
文献类型：
--
作者：
Ohmori, Yuki;Morioka, Motohiro;Kuratsu, Jun-ichi
背景技术背景：粒细胞集落刺激因子（G-CSF）动员造血骨髓细胞进入体循环，临床上用于治疗化疗引起的中性粒细胞减少症。最近，G-CSF被证明在急性脑梗塞中具有神经保护和血管生成作用。目的：评价G-CSF对间接旁路手术后血管生成的影响。方法：通过永久性双侧颈内动脉闭塞（BIAO）在雄性Wistar大鼠中诱导慢性脑低灌注。BICAO后，进行单侧间接转流和脑血管新生术（EGS），并连续5天肌肉注射人重组G-CSF（10 μ g/kg）或生理盐水。结果：BICAO组局部脑血流量下降至对照组的62.52% ± 5.8%（P <0.01）。BICAO后21天，除G-E组外，所有治疗组的rCBF均显著增加（n = 10; P <0.05）。G+E+组的rCBF增加显著高于其他组。G-CSF和EGS治疗均显著增加小血管数（P <0.01），G-CSF和EGS在增加小血管数方面具有相加作用。结论：G-CSF和间接转流术联合应用可诱导脑慢性低灌注状态下rCBF和血管生成增加。这是第一份报告，证明G-CSF可以增强间接旁路手术诱导的血管生成，这种联合治疗是一种安全和简单的治疗方法。
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic bone marrow cells into systemic circulation and has been used clinically to treat chemotherapy-induced neutropenia. Recently, G-CSF was shown to have neuroprotective and angiogenetic effects in acute cerebral infarction.OBJECTIVE: To evaluate the effects of G-CSF for angiogenesis after indirect bypass surgery.METHODS: Chronic cerebral hypoperfusions were induced in male Wistar rats by permanent bilateral internal carotid artery occlusion (BICAO). After BICAO, unilateral indirect bypass and encephalogaleosynangiosis (EGS) were performed, and human recombinant G-CSF (10 mu g/kg) or saline was injected intramuscularly for 5 consecutive days. We measured regional cerebral blood flow (rCBF) by laser Doppler flowmetry and performed immunohistochemical analysis 21 days after BICAO.RESULTS: BICAO decreased rCBF to 62.52% +/- 5.8% of control (P < .01). The rCBF increased significantly 21 days after BICAO in all treatment groups (n = 10; P < .05) except the G-E-group. The rCBF increase observed in the G+E+ group was significantly higher than that observed in other groups. Both G-CSF and EGS treatments significantly increased the number of small vessels (P < .01), and G-CSF and EGS showed additive effect in increasing the number of small vessels.CONCLUSION: Combined use of G-CSF and indirect bypass surgery induces an increase in rCBF and angiogenesis under conditions of cerebral chronic hypoperfusion. This is the first report to demonstrate that G-CSF can enhance angiogenesis induced by indirect bypass surgery, and that this combined therapy is a safe and easy method of treatment.