Hemorrhagic transformation (HT) has been claimed to represent the most feared complication of treatment with intravenous tissue plasminogen activator (t-PA) therapy. In this study, we tested the effect of rosiglitazone on HT in a rat focal cerebral ischemia model. Male Sprague-Dawley rats received an injection of 50% dextrose (6ml/kg intraperitoneally) and were subjected to middle cerebral artery occlusion (MCAO) 10 min later, with the regional cerebral blood flow monitored in vivo by laser-Doppler-flowmetry. Two groups were included: rosiglitazone treatment and vehicle group. In the treatment group, after 1.5h of ischemia, rosiglitazone (2mg/kg) was administered at the onset of reperfusion. Neurobehavioral scores, infarct volume, hemoglobin leakage, hemorrhage rate, the expression of collagen IV and glucose transporter 1 (GLUT1) were measured at 24h after ischemia. Rosiglitazone improved neurobehavioral deficits, reduced infarct volume and hemorrhage rate, and inhibited hemoglobin leakage, when compared with the vehicle group. In addition, it increased the expression of collagen IV and GLUT1 compared to the vehicle group. Our results suggest that rosiglitazone attenuated the hyperglycemia-induced HT after MCAO, possibly by preservation of GLUT1 expression.
Keywords: 2,3,5-triphenyltetrazolium chloride; BBB; GLUT1; HI-1; HI-2; HT; MCAO; PBS; PH-1; PH-2; PPARγ; TTC; blood–brain barrier; glucose transporter 1; hemorrhagic infarction type 1; hemorrhagic infarction type 2; hemorrhagic transformation; hyperglycemia; middle cerebral artery occlusion; parenchymal hemorrhage type 1; parenchymal hemorrhage type 2; peroxisome proliferator-activated receptor gamma; phosphate buffered saline; rCBF; regional cerebral blood flow; rosiglitazone; t-PA; tissue plasminogen activator.
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