Coupling of angiogenesis and neurogenesis in cultured endothelial cells and neural progenitor cells after stroke
Open accessAbstract
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.
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Microvessels and neuroblasts mutually support each other via release of trophic factors, resulting in a tight interplay that stimulates brain remodelling, reduces delayed neuronal degeneration, promotes neuronal plasticity, modulates glial responses, and attenuates brain inflammation.
“Microvessels and neuroblasts mutually support each other via release of trophic factors, resulting in a tight interplay that stimulates brain remodelling processes, reducing delayed neuronal degeneration,14,45 promoting neuronal plasticity,15 modulating glial responses,14,46 and attenuating brain inflammation14,46 (figure 2).”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [45]
The finding that neural precursor cells prevent ischaemic injury and promote neurological recovery could be attributed to bystander effects from interaction of neuroblasts with microvasculature near the lesion, creating an environment that promotes brain remodelling.
“The finding that neural precursor cells prevent ischaemic injury and promote neurological recovery could be attributed to bystander effects related to the interaction of neuroblasts with the microvasculature in the vicinity of the ischaemic lesion, which creates an environment that promotes brain remodelling (figure 2).14,15,37,45”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [45]
Neuroblasts reinforce angiogenesis via release of VEGF.
“Importantly, neuroblasts also reinforce angiogenesis via release of VEGF.45”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [45]
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References 33 · Cited by 254
- Authors
- Teng, H., Zhang, Z. G., Wang, L., Zhang, R. L., Zhang, L., Morris, D., Gregg, S. R., Wu, Z., Jiang, A., Lu, M., Zlokovic, B. V., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan, USA
- Departments of Neurosurgery and Neurology, University of Rochester Medical Center, Rochester, New York, USA
- Corresponding author
- Zhang, Zheng Gang
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2007-10-31
- Volume
- 28
- Issue
- 4
- Pages
- 764-771
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC2744583
- OpenAlex
- W2079365338
- Cited by
- 254
- References
- 33
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 13 · 2023: 8 · 2022: 12 · 2021: 14 · 2020: 16 · 2019: 15 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 21 · 2014: 15 · 2013: 18 · 2012: 15
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL064766, R01HL64766)
- National Institute of Neurological Disorders and Stroke (P01NS23393, P01NS023393, P01NS42345, R01 NS 38292, P01NS042345, R01NS038292)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- angiogenesis, neurogenesis, stroke, brain endothelial cells, neural progenitor cells, subventricular zone, ischemia, neuronal differentiation, astrocyte differentiation, capillary tube formation, vascular endothelial growth factor, VEGFR2, conditioned medium, co-culture
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Image Processing, Computer-Assisted, Male, Neovascularization, Pathologic, Neurons, Stem Cells, Blotting, Western, Culture Media, Conditioned, Rats, Wistar, Coculture Techniques, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, Stroke, Endothelial Cells, Cell Proliferation, Rats, Caspase 3
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