title: VEGF enhance cortical newborn neurons and their neurite development in adult rat brain after cerebral ischemia.
abstract: To study the effect of VEGF overexpression on development of cortical newborn neurons in the brains after stroke, we injected human VEGF(165)-expressive plasmids (phVEGF) into the lateral ventricle of rat brains with a transient middle cerebral artery occlusion (MCAO). An injection of phVEGF significantly promoted angiogenesis (BrdU(+)-von Willebrand's factor(+)) and reduced infarct volume in the rat brain after MCAO. Single labeling of 5'-bromodeoxyuridine (BrdU) and double staining of BrdU with lineage-specific neuronal markers were used to indicate the proliferated cells and maturation of newborn neurons in the brain section of rats at 2, 4, and 8 weeks after MCAO. The results showed that BrdU positive (BrdU(+)) cells existed in ipsilateral frontal cortex within 8 weeks after MCAO and reached the maximum at 2 weeks of reperfusion. The phVEGF treatment significantly increased BrdU(+) cells compared with the control plasmid (pEGFP) injection. Cortical neurogenesis was indicated by the presence of newborn immature (BrdU(+)-Tuj1(+)), newborn mature (BrdU(+)-MAP-2(+)), and newborn GABAergic (BrdU(+)-GAD67(+)) neurons. All these neurons declined within 8 weeks after MCAO in the controls. Injection of phVEGF significantly increased BrdU(+)-Tuj1(+) neurons at 2 weeks, and BrdU(+)-MAP-2(+) neurons and BrdU(+)-GAD67(+) neurons at 4 and 8 weeks, respectively after MCAO. Moreover, phVEGF treatment significantly increased neurite length and branch numbers of BrdU(+)-MAP-2(+) newborn neurons compared with pEGFP treatment. These results demonstrate that VEGF enhances maturation of stroke-induced cortical neurogenesis and dendritic formation of newborn neurons in adult mammalian brains.
authors.affiliation: Department of Neurobiology, Institute for Biomedical Science, Shanghai Medical College of Fudan University, PR China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Wang
authors.forename: Hui-Ru
authors.initials: HR
authors.lastname: Cui
authors.forename: Shan-Zheng
authors.initials: SZ
authors.lastname: Yang
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Sun
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: D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites; D015153:Blotting, Western; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018613:Microscopy, Confocal; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D000963:Antimetabolites; D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A; D001973:Bromodeoxyuridine