Cited by 287Neurogenesis and neuroplasticity mechanismsAngiogenesis and VEGF in CancerNeurological Disease Mechanisms and Treatments

Endothelial nitric oxide synthase regulates brain-derived neurotrophic factor expression and neurogenesis after stroke in mice

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Chen, Jieli, Zacharek, Alex, Zhang, Chunling, Jiang, Hao, Li, Yi, Roberts, Cynthia, Lu, Mei, Kapke, Alissa +1 more·2005·The Journal of Neuroscience

Abstract

Here, we investigate the effects of endothelial nitric oxide synthase (eNOS) on angiogenesis, neurogenesis, neurotrophic factor expression, and neurological functional outcome after stroke. Wild-type and eNOS knock-out ( eNOS -/- ) mice were subjected to permanent occlusion of the right middle cerebral artery. eNOS -/- mice exhibited more severe neurological functional deficit after stroke than wild-type mice. Decreased subventricular zone (SVZ) progenitor cell proliferation and migration, measured using bromodeoxyuridine, Ki-67, nestin, and doublecortin immunostaining in the ischemic brain, and decreased angiogenesis, as demonstrated by reduced endothelial cell proliferation, vessel perimeter, and vascular density in the ischemic border, were evident in eNOS -/- mice compared with wild-type mice. eNOS-deficient mice also exhibited a reduced response to vascular endothelial growth factor (VEGF)-induced angiogenesis in a corneal assay. ELISAs showed that eNOS -/- mice have decreased brain-derived neurotrophic factor (BDNF) expression but not VEGF and basic fibroblast growth factor in the ischemic brain compared with wild-type mice. In addition, cultured SVZ neurosphere formation, proliferation, telomerase activity, and neurite outgrowth but not cell viability from eNOS -/- mice were significantly reduced compared with wild-type mice. BDNF treatment of SVZ cells derived from eNOS -/- mice restored the decreased neurosphere formation, proliferation, neurite outgrowth, and telomerase activity in cultured eNOS -/- SVZ neurospheres. SVZ explant cell migration also was significantly decreased in eNOS -/- mice compared with wild-type mice. These data indicate that eNOS is not only a downstream mediator for VEGF and angiogenesis but also regulates BDNF expression in the ischemic brain and influences progenitor cell proliferation, neuronal migration, and neurite outgrowth and affects functional recovery after stroke.

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Crossref · 10.1523/jneurosci.5071-04.2005

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Authors
Chen, J., Zacharek, A., Zhang, C., Jiang, H., Li, Y., Roberts, C., Lu, M., Kapke, A., & Chopp, M.
Affiliations
  • Henry Ford Health (US)
  • Oakland University (US)
Corresponding author
Chopp, Michael
Venue
The Journal of Neuroscience
Published
2005-03-02
Volume
25
Issue
9
Pages
2366-2375
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1987444038
Cited by
287
References
57
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 16 · 2020: 13 · 2019: 8 · 2018: 14 · 2017: 14 · 2016: 12 · 2015: 24 · 2014: 25 · 2013: 18 · 2012: 17
FWCI
4.99
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS047682, P01NS023393)
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 › Neurological Disease Mechanisms and Treatments
Keywords
endothelial nitric oxide synthase, brain-derived neurotrophic factor, stroke, neurogenesis, angiogenesis, neurosphere formation, telomerase activity, neurite outgrowth, vascular endothelial growth factor, neuronal migration, neurological recovery, middle cerebral artery occlusion, ischemic brain
MeSH terms
Doublecortin Domain Proteins, Animals, Blood Pressure, Brain, Bromodeoxyuridine, Cell Count, Cell Movement, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Intermediate Filament Proteins, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Naphthalenes, Nerve Tissue Proteins, Neurologic Examination, Neuropeptides, Oxepins, Psychomotor Performance, Time Factors, Gene Expression, Neurites, Corneal Neovascularization, Mice, Knockout, Telomerase, Brain-Derived Neurotrophic Factor, Ki-67 Antigen, Recovery of Function, Infarction, Middle Cerebral Artery, Vascular Endothelial Growth Factor A, Endothelial Cells, Cell Proliferation, Mice, Nitric Oxide Synthase Type III, Nestin

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