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Transl Stroke Res. 2012 Sep;3(3):390-6. doi: 10.1007/s12975-012-0190-9. Epub 2012 May 15.

Acute rosiglitazone treatment during reperfusion after hyperglycemic stroke is neuroprotective not vascular protective.

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1
Departments of Neurology, Obstetrics, Gynecology & Reproductive Sciences, and Pharmacology, University of Vermont College of Medicine.

Abstract

Reperfusion therapy for ischemic stroke can cause secondary brain injury, especially under hyperglycemic (HG) conditions. Here we investigated the effect of acute treatment with rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist, prior to postischemic reperfusion, on stroke outcome during HG stroke. Male Wistar rats that were either normoglycemic (NG) or HG by STZ (50 mg/kg; for 5-6 days) underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Animals were treated i.v. with rosiglitazone (1mg/kg; n=16), rosiglitazone (1mg/kg) + the free radical scavenger Tempol (50mg/kg; n=10) or vehicle (n=16) ten minutes prior to reperfusion and infarct volume, edema formation and cerebral blood flow (CBF) were measured. Compared to NG, HG stroke significantly increased infarct volume from 5.2±3.0% vs. 14.7±3.6% (p<0.05). Rosiglitazone prevented the increased infarct volume induced by HG that was only 6.9±2.0% (p<0.05 vs. HG) but did not have any effect on edema formation that was increased by 3.0% in both HG vehicle and rosiglitazone-treated ipsilateral vs. contralateral hemispheres (p<0.05). Combined treatment of rosiglitazone + Tempol did not significantly change brain water content that remained 2.2% greater than contralateral (p<0.05), but reversed the neuroprotective properties of rosiglitazone in HG MCAO animals such that infarct volume was 14.3±4.4% (p>0.05 vs. vehicle). The lack of an effect of combined treatment of rosiglitazone + Temple may be due to a decrease in reperfusion CBF that was only 60% of baseline (p<0.01) compared to 82% and 89% for HG vehicle and rosiglitazone treated animals (p>0.05). In conclusion, acute rosiglitazone treatment prior reperfusion was neuroprotective but not vascular protective during HG stroke.

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