Microglial ROS production in an electrical rat post-status epilepticus model of epileptogenesis

Microglial ROS production in an electrical rat post-status epilepticus model of epileptogenesis
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电大鼠癫痫发作后模型中小胶质细胞 ROS 的产生

DOI:
10.1016/j.neulet.2015.05.041
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发表时间:
2015
影响因子:
2.5
通讯作者:
H Potschka
H Potschka
中科院分区:
医学4区
文献类型:
--
作者:
Rettenbeck ML;Rüden EL;Bienas S;Carlson R;Stein VM;Tipold A;H Potschka

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活性氧和炎症信号已被认为是导致癫痫发生的关键病理生理因素。考虑到具有抗癫痫潜能的抗炎和抗氧化联合治疗策略的发展,表征癫痫发生过程中小胶质细胞活性氧产生的时间进程是主要感兴趣的。因此,我们分离了小胶质细胞,并用流式细胞术分析了癫痫持续状态后两天大鼠模型中活性氧的产生。癫痫持续状态两天后,一个大型细胞团在佛波酯-肉豆蔻-醋酸酯刺激下表现出明显的反应,产生了过量的活性氧。无论是在潜伏期还是在自发性癫痫发作的慢性期,都没有发现具有诱导活性氧物种的可比细胞群。我们能够在癫痫持续状态后的电击大鼠模型中证明,小胶质细胞ROS的产生在初始发作后达到峰值,仅在潜伏期略有增加,并在慢性癫痫阶段恢复到对照水平。这些数据表明,抗炎和激进清除方法的结合可能只在致痫脑损伤后的短时间内才有好处。
Reactive oxygen species and inflammatory signaling have been identified as pivotal pathophysiological factors contributing to epileptogenesis. Considering the development of combined anti-inflammatory and antioxidant treatment strategies with antiepileptogenic potential, a characterization of the time course of microglial reactive oxygen species generation during epileptogenesis is of major interest. Thus, we isolated microglia cells and analyzed the generation of reactive oxygen species by flow cytometric analysis in an electrical rat post-status epilepticus model.Two days post status epilepticus, a large-sized cell cluster exhibited a pronounced response with excessive production of reactive oxygen species upon stimulation with phorbol-myristate-acetate. Neither in the latency phase nor in the chronic phase with spontaneous seizures a comparable cell population with induction of reactive oxygen species was identified.We were able to demonstrate in the electrical rat post-status-epilepticus model, that microglial ROS generation reaches a peak after the initial insult, is only marginally increased in the latency phase, and returns to control levels during the chronic epileptic phase. The data suggest that a combination of anti-inflammatory and radical scavenging approaches might only be beneficial during a short time window after an epileptogenic brain insult.
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