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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Peroxisome proliferator-activated receptor gamma promotes neuroprotection by modulating cyclic D1 expression after focal cerebral ischemia.
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Peroxisome proliferator-activated receptor gamma promotes neuroprotection by modulating cyclic D1 expression after focal cerebral ischemia.

机译:过氧化物酶体增殖物激活的受体γ通过调节局灶性脑缺血后的循环D1表达来促进神经保护。

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摘要

Peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to protect against stroke and improve neurological outcome after cerebral ischemia. This study investigated whether activation of cerebral PPARgamma improves recovery from focal cerebral ischemia by reducing expression of cyclin D1, which is associated with programmed neuron death. Focal cerebral ischemia was induced by 90 min of middle cerebral artery occlusion (MCAO), followed by reperfusion. Intracerebroventricular (i.c.v.) infusion of the PPARgamma agonist ciglitazone, beginning 5 days before and continuing through 1 day after MCAO, reduced infarct size and cyclin D1 expression in the peri-infarct cortical region. Furthermore, primary cortical neurons treated with ciglitazone showed suppressed expression of cyclin D1 in response to hypoxia-reoxygenation. This protective effect was reversed after cotreatment with the selective PPAR-gamma antagonist GW 9662 (2-chloro-5-nitrobenzanilide), clearly demonstrating the involvement of a PPARgamma-dependent mechanism. Our data provide evidence that activation of neuronal PPARgamma makes a substantial contribution to neuroprotection by preventing cyclin D1 up-regulation in vitro and in vivo.
机译:过氧化物酶体增殖物激活受体γ(PPARgamma)已被证明可以预防中风并改善脑缺血后的神经功能。这项研究调查了大脑PPARγ的激活是否通过减少细胞周期蛋白D1的表达来改善局灶性脑缺血的恢复,而细胞周期蛋白D1的表达与程序性神经元死亡有关。 90分钟的大脑中动脉闭塞(MCAO)诱发局灶性脑缺血,然后再灌注。脑室内(i.c.v.)输注PPARgamma激动剂西格列酮,从MCAO开始前5天开始,一直持续到1天,直到梗塞周围皮层区域梗死面积减小,cyclin D1表达降低。此外,西格列酮治疗的原代皮层神经元对缺氧-复氧反应显示出抑制的细胞周期蛋白D1表达。与选择性PPAR-γ拮抗剂GW 9662(2-氯-5-硝基苯甲酰苯胺)共同处理后,这种保护作用被逆转,清楚地证明了PPAR-γ依赖性机制的参与。我们的数据提供了证据,表明神经元PPARgamma的激活通过阻止细胞周期蛋白D1在体外和体内的上调而对神经保护做出了重大贡献。

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