Original Article| Volume 23, ISSUE 6, P1429-1439, July 2014

Rosuvastatin Ameliorates Early Brain Injury after Subarachnoid Hemorrhage via Suppression of Superoxide Formation and Nuclear Factor-Kappa B Activation in Rats


      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.


      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.


      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.


      The present study demonstrates that rosuvastatin pretreatment ameliorates EBI after SAH through the attenuation of oxidative stress and NF-κB–mediated inflammation.

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