Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke

Ann Neurol. 2003 Jun;53(6):743-51. doi: 10.1002/ana.10555.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Atorvastatin
  • Brain / blood supply*
  • Brain / drug effects*
  • Brain / pathology
  • Enzyme Inhibitors / pharmacology
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Immunohistochemistry
  • Male
  • Mitogen-Activated Protein Kinases / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neovascularization, Physiologic / drug effects
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Phosphorylation / drug effects
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins c-akt
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use*
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Stroke / drug therapy*
  • Stroke / immunology
  • Stroke / pathology
  • Synapses / drug effects*
  • Vascular Endothelial Growth Factor Receptor-2 / immunology

Substances

  • Antibodies
  • Enzyme Inhibitors
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Proto-Oncogene Proteins
  • Pyrroles
  • Atorvastatin
  • Nitric Oxide Synthase
  • Vascular Endothelial Growth Factor Receptor-2
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • NG-Nitroarginine Methyl Ester