Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke.
Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.
Teng
Hua
H
Department of Neurology, Henry Ford Health System, Detroit, Michigan 48202, USA.
Zhang
Zheng Gang
ZG
Wang
Lei
L
Zhang
Rui Lan
RL
Zhang
Li
L
Morris
Dan
D
Gregg
Sara R
SR
Wu
Zhenhua
Z
Jiang
Angela
A
Lu
Mei
M
Zlokovic
Berislav V
BV
Chopp
Michael
M
D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007091:Image Processing, Computer-Assisted; D020287:In Situ Nick-End Labeling; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020521:Stroke / Q000503:physiopathology*
D017077:Culture Media, Conditioned; D053148:Caspase 3