Effects of Pravastatin on neuroprotection and neurogenesis after cerebral ischemia in rats.

OBJECTIVE

Statins inhibit hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity and lower total serum cholesterol levels. We investigated the effects of Pravastatin on neuroprotection and neurogenesis in the dentate gyrus (DG), subventricular zone (SVZ) and striatum after cerebral ischemia in rats.

METHODS

The filament method was used for temporary middle cerebral artery occlusion (tMCAO). Pravastatin or saline post-ischemically were administered at subsequent time points: 6 h after tMCAO, and then on every subsequent day up to day 14 after tMCAO. Neurological outcome was investigated by using a neuroscore, the beam balance test and the rotarod test. Cholesterol and triglycerides levels were determined by blood sample analysis prior to sacrifice. Infarct area was calculated by microtubule-associated protein 2 (MAP2) staining. Neurogenesis was evaluated by triple staining with bromodeoxyuridine (BrdU), doublecortin (DCX), and neuronal nuclei (NeuN).

RESULTS

Compared with the control groups, Pravastatin treated animals were significantly improved in neurological outcome in rotarod test, with smaller infarct size. Pravastatin increased BrdU-positive cells number in the DG (P = 0.0029) and the SVZ (P = 0.0280) but not in the striatum (P = 0.3929). Furthermore, Pravastatin increased BrdU-labeled DCX positive cells number in the DG (P = 0.0031), SVZ (P = 0.0316) and striatum (P = 0.0073). We also observed a DCX-positive cells stream from the SVZ to the striatum, suggesting a migration route of those immature neurons. No significant differences of total serum cholesterol and triglycerides were observed between groups.

CONCLUSIONS

The Pravastatin administration strategy is safe and could promote neurological recovery in ischemic stroke. Pravastatin induces neurogenesis in the DG and SVZ, and increases the number of migration cells in the striatum. These effects are independent of the cholesterol-lowering property of Pravastatin.