期刊
NEUROCHEMISTRY INTERNATIONAL
卷 55, 期 7, 页码 629-636出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2009.06.007
关键词
Adult brain injury; Cerebral vascular disease; Neuroplasticity; Regeneration; Stroke
资金
- National Basic Research Program of China [2006CB504100, 2006CB943702]
- Natural Science Foundation of China [30770660]
- Chinese Ministry of Education [2003-24]
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. (C) 2009 Elsevier Ltd. All rights reserved.
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