title: VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration.
abstract: New neurons are generated continuously in the subventricular zone and dentate gyrus of the adult brain. Neuropathologic processes, including cerebral ischemia, can enhance neurogenesis, as can growth factors and other physiologic stimuli. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can promote neurogenesis, but it is unknown whether VEGF can enhance migration of newborn neurons toward sites of ischemic injury, where they might be able to replace neurons that undergo ischemic death. In the present study we produced permanent focal cerebral ischemia in transgenic (Tg) mice that overexpress VEGF. Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (Brdu) labeling and immunostaining for cell type-specific markers. In VEGF-Tg mice, brains examined 7-28 days after cerebral ischemia showed markedly increased subventricular zone (SVZ) neurogenesis, chains of neuroblasts extending from the SVZ to the peri-infarct cortex, and an increase in the number of newly generated cortical neurons at 14-28 days after ischemia. In concert with these effects, VEGF overexpression reduced infarct volume and improved postischemic motor function. These findings provide evidence that VEGF increases SVZ neurogenesis and neuromigration, consistent with a possible role in repair. Our data suggest that in addition to its neuroprotective effects, which are associated with improved outcome in the acute phase after cerebral ischemia, VEGF enhances postischemic neurogenesis, which could provide a therapeutic target for more chronic brain repair.
authors.affiliation: Buck Institute for Age Research, Novato, California 94945, USA.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Wang
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Mao
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Surita
authors.initials: S
authors.lastname: Banwait
authors.forename: Hugo H
authors.initials: HH
authors.lastname: Marti
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine