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VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion
Author(s) -
Wang YongQuan,
Guo Xin,
Qiu MeiHong,
Feng XiaoYuan,
Sun FengYan
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21091
Subject(s) - neurogenesis , bromodeoxyuridine , angiogenesis , vascular endothelial growth factor , striatum , neuroprotection , medicine , stroke (engine) , endocrinology , biology , neuroscience , immunohistochemistry , dopamine , vegf receptors , mechanical engineering , engineering
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. © 2006 Wiley‐Liss, Inc.