Cited by 538Neurogenesis and neuroplasticity mechanismsNeurological Disorders and TreatmentsStroke Rehabilitation and Recovery

Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke

Chen, Jieli, Zhang, Zheng Gang, Li, Yi, Wang, Ying, Wang, Lei, Jiang, Hao, Zhang, Chenling, Lu, Mei +3 more·2003·Annals of Neurology

Abstract

We demonstrate that the 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors atorvastatin and simvastatin enhance functional outcome and induce brain plasticity when administered after stroke to rats. With atorvastatin treatment initiated 1 day after stroke, animals exhibited significant increases in vascular endothelial growth factor, cyclic guanosine monophosphate, angiogenesis, endogenous cell proliferation and neurogenesis, and an increase in the synaptic protein, synaptophysin. Atorvastatin‐induced angiogenesis in a tube formation assay was reduced by an antibody against the vascular endothelial growth factor receptor 2 (FIK‐1) and by the nitric oxide synthase inhibitor, N ‐mono‐methyl‐ L ‐arginine (L‐NAME). Atorvastatin also induced phosphorylation of Akt and Erk in cultured primary cortical neurons. These data indicate that atorvastatin induced brain plasticity and has neurorestorative activity after experimental stroke. Ann Neurol 2003

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Crossref · 10.1002/ana.10555

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Authors
Chen, J., Zhang, Z. G., Li, Y., Wang, Y., Wang, L., Jiang, H., Zhang, C., Lu, M., Katakowski, M., Feldkamp, C. S., & Chopp, M.
Affiliations
Henry Ford Health (US)
Corresponding author
Chopp, Michael
Venue
Annals of Neurology
Publisher
Wiley
Published
2003-05-27
Volume
53
Issue
6
Pages
743-751
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2106578597
Cited by
538
References
38
Citations by year
2026: 4 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 11 · 2019: 13 · 2018: 17 · 2017: 17 · 2016: 33 · 2015: 31 · 2014: 29 · 2013: 34 · 2012: 36
FWCI
7.23
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns035504-03)
  • National Heart, Lung, and Blood Institute (R01HL064766)
  • National Institute of Neurological Disorders and Stroke (R01-NS35504, P01NS023393)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
  • Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
Keywords
statins, atorvastatin, simvastatin, stroke, angiogenesis, neurogenesis, synaptogenesis, neuroplasticity, neurorestoration, vascular endothelial growth factor, VEGFR2, nitric oxide synthase, L-NAME, Akt phosphorylation, ERK1/2 phosphorylation, synaptophysin, cell proliferation, functional recovery
MeSH terms
Atorvastatin, Animals, Antibodies, Brain, Enzyme Inhibitors, Heptanoic Acids, Immunohistochemistry, Male, Neuronal Plasticity, Neurons, Phosphorylation, Proto-Oncogene Proteins, Pyrroles, Synapses, Signal Transduction, Rats, Wistar, Protein Serine-Threonine Kinases, Neovascularization, Physiologic, Nitric Oxide Synthase, Hydroxymethylglutaryl-CoA Reductase Inhibitors, NG-Nitroarginine Methyl Ester, Stroke, Mitogen-Activated Protein Kinases, Vascular Endothelial Growth Factor Receptor-2, Proto-Oncogene Proteins c-akt, Rats

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