Therapeutic effects of a combinatorial treatment of simvastatin and bone marrow stromal cells on experimental embolic stroke

Basic Clin Pharmacol Toxicol. 2012 Jun;110(6):487-93. doi: 10.1111/j.1742-7843.2011.00848.x. Epub 2012 Jan 20.

Abstract

In this study, we investigated the therapeutic effects of simvastatin administered in combination with bone marrow stromal cells (BMSCs) following experimentally induced embolic stroke in rats. Effects on infarct volume, brain oedema and neurological deficits were examined. Focal ischaemic brain injury was induced by emblazing a preformed clot into the middle cerebral artery in rats. Animals were administered simvastatin (40 mg/kg) at 1 hr after stroke, or BMSCs (3 × 10(6)) at 24 hr after stroke or a combination of these two treatments. Rats receiving a dose of simvastatin in combination with BMSC administration demonstrated a significant reduction in neurological deficits, a significant reduction in infarct volume and a significant decrease in brain oedema. Our data show that combining simvastatin administration with BMSCs has an additive effect on improving functional outcome in this thromboembolic stroke model.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biomarkers / analysis
  • Bone Marrow Transplantation*
  • Brain Edema / etiology
  • Brain Edema / prevention & control
  • Cells, Cultured
  • Combined Modality Therapy
  • Disease Models, Animal
  • Fibronectins / analysis
  • Hyaluronan Receptors / analysis
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / therapy*
  • Leukocyte Common Antigens / analysis
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Wistar
  • Recovery of Function
  • Simvastatin / pharmacology*
  • Stroke / etiology
  • Stroke / pathology
  • Stroke / physiopathology
  • Stroke / therapy*
  • Stromal Cells / chemistry
  • Stromal Cells / transplantation*
  • Time Factors

Substances

  • Biomarkers
  • Fibronectins
  • Hyaluronan Receptors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Leukocyte Common Antigens
  • Ptprc protein, rat