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Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke
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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“Neurogenesis is stimulated in response to stroke and is substantially amplified by therapeutic interventions that promote functional recovery.33–36”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [36]
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“Statins also have neurorestorative properties (ie, promotion of neuronal survival, angiogenesis, and neurogenesis).36,89”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [36]
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Metadata
- 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 › Neuroprotection in Cerebral Ischemia
- 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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