VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion
VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion
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DOI：
10.1002/jnr.21091
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Sun, Feng-Yan
中科院分区：
文献类型：
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作者：
Wan, Yong-Quan;Guo, Xin;Sun, Feng-Yan
为了阐明血管内皮生长因子（VEGF）是否改善卒中诱导的纹状体神经发生，我们将人VEGF（165）表达质粒（phVEGF）与脂质体混合注入短暂大脑中动脉闭塞（MCAO）后的成年大鼠。结果显示，单次注射EGFP后2 h即出现阳性细胞，4 h进一步增强，3 d达高峰，14 d仍有阳性细胞。用phVEGF处理增加了血管生成，如通过vWF（内皮细胞的标志物）和5 '-溴脱氧尿苷（BrdU）（细胞增殖的标志物）的双重染色所示。在MCAO后2周，phVEGF治疗剂量依赖性地减少脑梗死体积。脑卒中后2 h内注射VEGF质粒可获得神经保护作用。此外，VEGF过表达显著增加了同侧SVZ中的细胞增殖以及MCAO同侧纹状体中的BrdU（+）-CRMP-4（+）和BrdU（+）-Tuj 1（+）（两种未成熟新生神经元的标记物）和BrdU（+）-MAP-2（+）（一种成熟新生神经元的标记物）细胞的数量。目前的研究结果表明，VEGF质粒治疗中风后，可以显着减少梗死体积和增强成年大鼠脑纹状体神经发生。这表明VEGF过表达在脑损伤中具有重要的神经元保护和修复功能，为脑卒中患者开发新的治疗策略提供了可能。(c)2006 Wiley-Liss，Inc.
To elucidate whether vascular endothelial growth factor (VEGF) improves stroke-induced striatal neurogenesis, we intraventricularly injected human VEGF(165)-expressive plasmid (phVEGF) mixed with liposome into adult rats after a transient middle cerebral artery occlusion (MCAO). The results showed that EGFP, a reporter protein, positive cells appeared at 2 hr, further enhanced at 4 hr, reached the maximum at 3 days and still remained at 14 days after a single injection. Treatment with phVEGF increased angiogenesis, as indicated by double staining of vWF, a marker of endothelial cells, and 5'-bromodeoxyuridine (BrdU), a marker of cell proliferation. The phVEGF treatment dose-dependently reduced infarct volume of brain at 2 weeks after MCAO. The neuroprotection by VEGF could be obtained when the plasmid was injected within 2 hr after stroke. Moreover, VEGF overexpression significantly increased cell proliferation in the ipsilateral SVZ and the numbers of BrdU(+)-CRMP-4(+) and BrdU(+)-Tuj1(+), two markers of immature newborn neurons, and BrdU(+)-MAP-2(+), a marker of mature newborn neurons, cells in the ipsilateral striatum to MCAO. Present results show that VEGF plasmid treatment after stroke can significantly reduce infarct volume and enhance striatal neurogenesis in adult rat brain. This suggests that VEGF overexpression acquires significant functions of neuronal protection and repair in the injured brain, which provides a possibility to develop a novel therapeutic strategy for the patients with stroke. (c) 2006 Wiley-Liss, Inc.