Edaravone enhances brain-derived neurotrophic factor production in the ischemic mouse brain.
Edaravone enhances brain-derived neurotrophic factor production in the ischemic mouse brain.
复制标题
DOI：
10.3390/ph8020176
复制
发表时间：
2015-04-02
期刊：
影响因子：
--
通讯作者：
Furukawa Y
中科院分区：
文献类型：
--
作者：
Okuyama S;Morita M;Sawamoto A;Terugo T;Nakajima M;Furukawa Y
依达拉奉是一种用于治疗中风的临床药物，通过其抗氧化活性在动物模型的缺血性脑中保护神经元细胞死亡和记忆丧失。在本研究中，我们皮下注射依达拉奉给小鼠，（3 mg/kg/天），并通过免疫组织化学分析显示依达拉奉（1）加速海马中脑源性神经营养因子（BDNF）的产生增加;（2）齿状回颗粒下区Doublecortin阳性神经元前体细胞增多;（3）抑制缺血诱导的海马钙-钙调蛋白依赖性蛋白激酶II的失活。我们还通过蛋白质印迹分析发现，依达拉奉（4）诱导cAMP反应元件结合（CREB）的磷酸化，CREB是一种调节BDNF基因表达的转录因子;（5）诱导细胞外信号调节激酶1/2的磷酸化，CREB的上游信号因子。这些结果表明，脑缺血后依达拉奉的神经保护作用不仅是通过消除氧化应激介导的，而且还通过诱导BDNF的产生。
Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day) for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1) accelerated increases in the production of brain-derived neurotrophic factor (BDNF) in the hippocampus; (2) increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3) suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4) induced the phosphorylation of cAMP response element-binding (CREB), a transcription factor that regulates BDNF gene expression; and (5) induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.