title: The role of VEGF/VEGFR2 signaling in peripheral stimulation-induced cerebral neurovascular regeneration after ischemic stroke in mice.
abstract: Ischemic stroke is a major cause of mortality and morbidity worldwide but effective treatments are limited. Strategies to enhance neurovascular remodeling following stroke provide promising opportunities to improve tissue repair and functional recovery. We have previously demonstrated that whisker activity promotes central angiogenesis in rodent models of whisker-barrel cortex stroke. However, the mechanisms involved in the regulation of neurovascular plasticity by peripheral stimulation are not well-defined. Here, we report that angiogenesis and neurogenesis occur concurrently after cerebral ischemia and whisker stimulation in mice. We show that neuroblasts expressing vascular endothelial growth factor receptor 2 (VEGFR2) migrate along the vessels. Blocking VEGFR2 with the selective inhibitor SU5416 (semaxinib) attenuates ischemia-induced regenerative responses and completely prevents whisker stimulation-induced neurovascular remodeling. These results suggest that VEGFR2-mediated signaling plays an important role in promoting post-ischemia neurovascular remodeling and provides a link between angiogenesis and neurogenesis.
authors.affiliation: Department of Neurology, Jiangsu Province Hospital of Traditional Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
authors.forename: Wen-Lei
authors.initials: WL
authors.lastname: Li
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Fraser
authors.forename: Shan P
authors.initials: SP
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Jiang
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018919:Neovascularization, Physiologic / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology*; D014738:Vibrissae / Q000294:innervation
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2