J Korean Neurosurg Soc.  2011 Nov;50(5):403-408. 10.3340/jkns.2011.50.5.403.

Prior Use of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Inhibitor, Simvastatin Fails to Improve Outcome after Experimental Intracerebral Hemorrhage

Affiliations
  • 1Department of Neurosurgery, National Medical Center, Seoul, Korea.
  • 2Department of Neurosurgery, Hanyang University Medical Center, Seoul, Korea. hjyi8499@hanyang.ac.kr
  • 3Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul, Korea.

Abstract


OBJECTIVE
Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) in vivo suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH.
METHODS
Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured.
RESULTS
Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy.
CONCLUSION
The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.

Keyword

Inflammation; Intracerebral hemorrhage; Neuroprotection; Outcome; Rat; Statins

MeSH Terms

Animals
Atrophy
Brain
Brain Edema
Caspase 3
Cell Death
Cerebral Hemorrhage
Hematoma
Inflammation
Microglia
Models, Animal
Nitric Oxide Synthase Type III
Oxidoreductases
Rats
Simvastatin
Caspase 3
Nitric Oxide Synthase Type III
Oxidoreductases
Simvastatin
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