Background
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been
suggested to possess pleiotropic effects, including antioxidant and anti-inflammatory
properties. We investigated the protective effects of pretreatment with rosuvastatin,
a relatively hydrophilic statin, on early brain injury (EBI) after a subarachnoid
hemorrhage (SAH), using the endovascular perforation SAH model.
Methods
Eighty-six male Sprague–Dawley rats were randomly divided into 3 groups: (1) sham
operation, (2) SAH + vehicle, and (3) SAH + 10 mg/kg rosuvastatin. Rosuvastatin or
vehicle was orally administered to rats once daily from 7 days before to 1 day after
the SAH operation. After SAH, we examined the effects of rosuvastatin on the neurologic
score, brain water content, neuronal cell death estimated by terminal deoxynucleotidyl
transferase–mediated uridine 5′-triphosphate nick end labeling staining, blood–brain
barrier disruption by immunoglobulin G (IgG) extravasation, oxidative stress, and
proinflammatory molecules.
Results
Compared with the vehicle group, rosuvastatin significantly improved the neurologic
score and reduced the brain water content, neuronal cell death, and IgG extravasation.
Rosuvastatin inhibited brain superoxide production, nuclear factor-kappa B (NF-κB)
activation, and the increase in activated microglial cells after SAH. The increased
expressions of tumor necrosis factor-alpha, endothelial matrix metalloproteinase-9,
and neuronal cyclooxygenase-2 induced by SAH were prevented by rosuvastatin pretreatment.
Conclusions
The present study demonstrates that rosuvastatin pretreatment ameliorates EBI after
SAH through the attenuation of oxidative stress and NF-κB–mediated inflammation.
Key Words
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Article info
Publication history
Published online: February 14, 2014
Accepted:
December 3,
2013
Received in revised form:
October 29,
2013
Received:
September 14,
2013
Footnotes
Grant information: Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (23390058). This work was also supported in part by a research grant from AstraZeneca.
The authors declare no competing financial interests.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.004
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
