Acute treatment with rosuvastatin protects obese mice against transient cerebral ischemia

Keita Mayanagi, Prasad V. Katakam, Tamas Gaspar, Ferenc Domoki, David W. Busija

Research output: Contribution to journalArticle

Abstract

Background and aims: Obesity is associated with significantly higher morbidity and mortality in stroke. Recent evidence indicates that acute treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is protective in stroke. Previously, we showed that 1-day treatment with rosuvastatin (RSV) can reverse impaired cerebrovascular responsiveness in insulin-resistant rats as effectively as with 4-weeks treatment (1). Whether short term statin therapy can reduce infarct volume following experimental stroke in insulin resistant or diabetic animals is unclear. The purpose of this study was to investigate the acute effects of RSV against transient focal cerebral ischemia in mice suffering from insulin resistance and obesity. Materials and Methods: Male 8 weeks old C57BL/6J ob/ob, lean and wild-type (WT) mice were treated with RSV (10 mg/kg/day, intraperitoneally) or vehicle for 3-days. Ischemia was induced by 60 minutes of middle cerebral artery occlusion (MCAO) using intraluminal suture method. Infarct volumes were measured 24 hours after reperfusion with TTC staining. In additional groups of animals, blood pressure and regional cerebral blood flow (rCBF) were monitored continuously through the 60 min MCAO procedure. Blood samples were withdrawn for measurement of blood glucose, total cholesterol, and insulin levels after the monitoring. Results: Blood glucose, total cholesterol and insulin levels were significantly elevated in ob/ob mice but were not affected by RSV. The rCBF reductions during MCAO were similar among all groups and were not affected by RSV. However, ob/ob mice exhibited a higher infarct volume compared to lean or WT. Furthermore, RSV significantly reduced infarct volume only in ob/ob mice (40.2 ± 2.7% vs. 31.7 ± 2.7%, p<0.05). Conclusion: Insulin resistance and obesity lead to vascular dysfunction (1) and elevated damage following strokes. However, treatment with statins provides rapid, beneficial effects prior to reductions in blood cholesterol levels.

Original languageEnglish
Pages (from-to)BP36-02W
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
Publication statusPublished - Nov 13 2007

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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