Allahtavakoli Mohammad, Moloudi Roohollah, Arababadi Mohammad Kazemi, Shamsizadeh Ali, Javanmardi Kazem
Department of Physiology, School of Medicine, Rafsanjan University of Medical Sciences, Shariati street, Rafsanjan, P.O.Box 77175-835, Iran.
Brain Res. 2009 May 19;1271:121-7. doi: 10.1016/j.brainres.2009.03.040. Epub 2009 Mar 28.
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.
罗格列酮（RGZ）是一种过氧化物酶体增殖物激活受体γ（PPAR-γ），已被证明在脑缺血急性期、创伤性或手术性脑损伤中具有神经保护和抗炎作用。然而，该化合物在缺血后延迟给药的效果仍不清楚。本研究旨在评估在栓塞性中风模型后24小时首次给予RGZ的神经保护作用。通过将预先形成的血栓置于大脑中动脉（MCA）来诱导大鼠栓塞性局灶性脑缺血。在MCA栓塞后24小时和48小时注射RGZ（5mg/kg，腹腔注射）。在中风后24、48和72小时评估神经功能缺损，然后分别采集血液和脑组织进行血细胞分类计数以及评估梗死体积和DNA片段化。与对照组相比，在脑缺血后24小时开始给予RGZ，可使梗死体积减少56%（P<0.05），并在脑缺血后72小时减少神经功能缺损（P<0.05）。此外，延迟给予RGZ可预防血液中的中性粒细胞增多（P<0.005），并在MCA闭塞72小时后显著减少DNA片段化（P<0.05）。因此，我们的数据表明，在中风后24小时开始用RGZ治疗可减少缺血性损伤、改善神经功能结局并预防中性粒细胞增多。这些发现可能支持这样一种观点，即RGZ对缺血性中风具有延长的治疗窗，因为它针对延迟的通路。
