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Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke
Author(s) -
Chen Jieli,
Zhang Zheng Gang,
Li Yi,
Wang Ying,
Wang Lei,
Jiang Hao,
Zhang Chenling,
Lu Mei,
Katakowski Mark,
Feldkamp Carolyn S.,
Chopp Michael
Publication year - 2003
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10555
Subject(s) - neurogenesis , atorvastatin , angiogenesis , synaptogenesis , vascular endothelial growth factor , protein kinase b , neuroprotection , endocrinology , medicine , chemistry , biology , microbiology and biotechnology , signal transduction , vegf receptors
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