Delayed post ischemic treatment with Rosiglitazone attenuates infarct volume, neurological deficits and neutrophilia after embolic stroke in rat

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma), has been shown to provide neuroprotective and anti-inflammatory effects in the acute phase of cerebral ischemia, and traumatic or surgical brain injuries. However, the effect of delayed post ischemia administration of this compound is still unclear. This study was designed to evaluate the neuroprotective effects of RGZ when first administered at 24 h after the embolic model of stroke. Embolic focal cerebral ischemia was induced in rats by placing a preformed clot into the middle cerebral artery (MCA). RGZ (5 mg/kg, intraperitoneally) was injected at 24 and 48 h after MCA embolization. Neurological deficits were evaluated at 24, 48 and 72 h after stroke, and blood and brain tissues were then collected for differential blood cell counts and assessments of infarct volume and DNA fragmentation, respectively. Compared to the control group, the administration of RGZ, starting 24 h after cerebral ischemia, reduced infarct volume by 56% (P < 0.05) and decreased neurological deficits at 72 h after cerebral ischemia (P < 0.05). Also, delayed administration of RGZ prevented neutrophilia in blood (P < 0.005) and significantly decreased DNA fragmentation (P < 0.05), 72 h after MCA occlusion. Therefore, our data demonstrate that treatment with RGZ, starting 24 h after stroke, can reduce ischemic injury, improve neurological outcome, and prevent neutrophilia. These findings may support the idea that RGZ has an extended therapeutic window for the treatment of ischemic stroke, as it targets delayed pathways. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.