Reduction of ischemic brain injury in rats with normothermic and hyperthermic conditions

J Neurosurg. 2008 Sep;109(3):522-9. doi: 10.3171/JNS/2008/109/9/0522.


Object: Statins have been used for induction of ischemic tolerance after cerebral ischemia. The authors have previously shown that simvastatin is protective after ischemic cerebral injury in normothermic conditions. In this study they further examined whether treatment with simvastatin can reduce ischemic brain injury in a hyperthermic condition.

Methods: Focal ischemic brain injury was induced by embolizing a preformed clot into the middle cerebral artery in rats. The authors initially examined whether treatment with simvastatin could reduce ischemic brain injury without or with hyperthermia. The infarct volume, edema, and neurological deficits were examined. They then studied whether simvastatin could reduce the perfusion deficits, damage to the blood-brain barrier (BBB), and degeneration of neurons in the ischemic injured brain.

Results: Simvastatin significantly reduced the infarct volume in both normothermic and hyperthermic conditions, compared with appropriate controls. Concomitantly, this treatment also significantly reduced neurological deficits and brain edema. Administration of simvastatin significantly decreased perfusion deficits, BBB permeability, and degenerated neurons.

Conclusions: These studies suggest that simvastatin is an effective agent for ischemic brain injury not only in normothermic but also in hyperthermic conditions, which may be through the decrease of BBB permeability, degenerated neurons, and perfusion deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control*
  • Cerebrovascular Circulation
  • Combined Modality Therapy
  • Disease Models, Animal
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hyperthermia, Induced*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Simvastatin / administration & dosage*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin