Acute neuroprotection by pioglitazone after mild brain ischemia without effect on long-term outcome
Acute neuroprotection by pioglitazone after mild brain ischemia without effect on long-term outcome
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DOI：
10.1016/j.expneurol.2008.12.007
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发表时间：
2009-04-01
影响因子：
5.3
通讯作者：
Endres, Matthias
中科院分区：
文献类型：
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作者：
Ji, Shengbo;Kronenberg, Golo;Endres, Matthias
过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂（噻唑烷二酮类）具有抗炎作用并改善内皮功能。在此，我们分析了吡格列酮对轻度短暂性脑缺血后短期和长期预后的影响。将129/SV小鼠进行30分钟的丝状大脑中动脉闭塞（MCAo），然后再灌注。事件后，每天腹膜内（i. p.）吡格列酮（20 mg/kg体重）或溶媒。短暂性脑缺血/再灌注后急性给予吡格列酮可在3天内减少缺血纹状体中损伤的大小和表达lba 1的小胶质细胞的数量。在体外，吡格列酮减弱原代小鼠小胶质细胞的迁移和增殖。然而，MCAo/再灌注后6周的分析不再产生吡格列酮对病变大小或lba 1+细胞计数的影响。关于功能性长期结局，我们也未检测到吡格列酮对杆试验或钢丝悬挂试验测量的运动功能或Morris水迷宫中的学习和记忆的有益作用。因此，我们的研究强调了将实验性中风研究扩展到长期结果分析的重要性。(c)2008年爱思唯尔公司All rights reserved.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists (thiazolidinediones) have anti-inflammatory effects and improve endothelium function. Here, we analyzed the effects of pioglitazone on short- and longer-term Outcome after mild transient brain ischemia. 129/SV mice were subjected to 30 min filamentous middle cerebral artery occlusion (MCAo), followed by reperfusion. Post event, animals were treated with daily intraperitoneal (i.p.) pioglitazone (20 mg/kg body weight) or vehicle. Pioglitazone given acutely after transient brain ischemia/reperfusion reduced lesion size and the number of lba1-expressing microglia in the ischemic striatum at three days. In vitro, pioglitazone attenuated migration and proliferation of primary mouse microglia. However, analysis at 6 weeks after MCAo/reperfusion no longer yielded an effect of pioglitazone on either lesion size or lba1+cell counts. Regarding functional longer-term outcome we also, did not detect a beneficial effect of pioglitazone on motor function measured either on the pole test or the wire hanging test or on learning and memory in the Morris water maze. Our study thus underscores the importance of extending experimental stroke studies to an analysis of longer-term outcome. (c) 2008 Elsevier Inc. All rights reserved.