The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
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]
In the citing paper
“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]
Citations
Cites
Running enhances neurogenesis, learning, and long-term potentiation in mice
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Chen, J., Li, Y., Wang, L., Zhang, Z., Lu, D., Lü, M., & Chopp, M. (2001) · Stroke · doi:10.1161/01.str.32.4.1005 · Cited by 1,770
Self-citationStructural mechanism for statin inhibition of HMG-CoA reductase
Istvan, E. S., & Deisenhofer, J. (2001) · Science · doi:10.1126/science.1059344 · Cited by 1,644
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Human marrow stromal cell therapy for stroke in rat
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Self-citationStatins Have Biphasic Effects on Angiogenesis
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Cited by
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Evidence for stroke-induced neurogenesis in the human brain
Jin, K., Wang, X., Xie, L., Mao, X. O., Zhu, W. P., Wang, Y., Shen, J., Mao, Y. Q., Banwait, S., & Greenberg, D. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603512103 · Cited by 644
Self-citationNeurorestorative therapies for stroke: underlying mechanisms and translation to the clinic
Zhang, Z. G., & Chopp, M. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70061-4 · Cited by 596
Self-citationAtorvastatin Induction of VEGF and BDNF Promotes Brain Plasticity after Stroke in Mice
Chen, J., Zhang, C., Jiang, H., Li, Y., Zhang, L., Robin, A. M., Katakowski, M., Lü, M., & Chopp, M. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600034 · Cited by 451
Self-citationEnhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APP Sw,Ind ) mice
Jin, K., Galván, V., Xie, L., Mao, X. O., Gorostiza, O. F., Bredesen, D. E., & Greenberg, D. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403678101 · Cited by 444
Tseng, M.-Y., Czosnyka, M., Richards, H. K., Pickard, J. D., & Kirkpatrick, P. J. (2005) · Stroke · doi:10.1161/01.str.0000176743.67564.5d · Cited by 412
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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