Rosuvastatin ameliorates early brain injury after subarachnoid hemorrhage via suppression of superoxide formation and nuclear factor-kappa B activation in rats.

Abstract

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.

• Authors: Ken Uekawa, Yu Hasegawa, Mingjie Ma, Takashi Nakagawa, Tetsuji Katayama, Daisuke Sueta, Kensuke Toyama, Keiichiro Kataoka, Nobutaka Koibuchi, Takayuki Kawano, Jun-ichi Kuratsu, Shokei Kim-Mitsuyama
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 23 Issue 6 Pg. 1429-39 (Jul 2014) ISSN: 1532-8511 [Electronic] United States
• PMID: 24529602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Fluorobenzenes
• NF-kappa B
• Neuroprotective Agents
• Pyrimidines
• Sulfonamides
• Superoxides
• Rosuvastatin Calcium

Topics

• Animals
• Apoptosis (drug effects)
• Brain (drug effects, metabolism, pathology)
• Brain Injuries (drug therapy, etiology, metabolism)
• Fluorobenzenes (pharmacology, therapeutic use)
• Male
• NF-kappa B (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Pyrimidines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Rosuvastatin Calcium
• Subarachnoid Hemorrhage (complications, drug therapy, metabolism)
• Sulfonamides (pharmacology, therapeutic use)
• Superoxides (metabolism)