title: VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion.
abstract: 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.
authors.affiliation: State Key Laboratory of Medical Neurobiology and Institute for Biomedical Science, Shanghai Medical College of Fudan University, Shanghai, Peoples Republic of China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Mei-Hong
authors.initials: MH
authors.lastname: Qiu
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Feng
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Sun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000473:pathology*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine