Ischemic postconditioning (PostC) is an endogenous neuroprotective strategy for cerebral ischemia induced by low activation of glutamate receptors. We have previously shown that the application of the mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine (DHPG) 5 min after 30 min of oxygen and glucose deprivation (OGD) reduces CA1 damage in organotypic hippocampal slices by activating the PI3K-Akt signalling pathway. In order to extend these data, we analysed the production of reactive oxygen species (ROS) and the glycogen synthase kinase 3β (GSK3β) signalling pathway. Our results show that DHPG PostC was associated with a reduction in the formation of ROS that is massively increased 24 h after OGD exposure. This reduction was prevented by the PI3K inhibitor LY294002, indicating that there is a link between the PI3K/Akt pathway and the formation of ROS in the protective mechanisms of PostC. DHPG PostC also induces a transient increased in GSK3β phosphorylation and inactivation that is followed by nuclear accumulation of β-catenin, that probably lead to the up-regulation of neuroprotective genes. Our results propose GSK3β as new target for neuroprotection, therefore, we verified that the two GSK3β inhibitors N-(3-Chloro-4-methylphenyl)-5-(4-nitrophenyl)-1,3,4-oxadiazol-2-amine (TC-G 24) and LiCl are neuroprotective agents in OGD and also can be used as PostC agents.

中文翻译：

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由（S）-3,5-二羟基苯甘氨酸后处理诱导的耐受性是由PI3K / Akt /GSK3β信号传导途径介导的脑缺血的体外模型。

缺血性后处理（PostC）是谷氨酸受体激活低引起的脑缺血的内源性神经保护策略。先前我们已经证明，缺氧和缺糖（OGD）30分钟后5分钟应用mGluR1 / 5激动剂（S）-3,5-二羟基苯基甘氨酸（DHPG）通过激活PI3K-可减少器官型海马切片中的CA1损伤。 Akt信号通路。为了扩展这些数据，我们分析了活性氧（ROS）和糖原合酶激酶3β（GSK3β）信号传导途径的产生。我们的结果表明，DHPG PostC与OGD暴露后24小时大量增加的ROS形成有关。PI3K抑制剂LY294002阻止了这种减少，表明在PostC的保护机制中，PI3K / Akt途径与ROS的形成之间存在联系。DHPG PostC还诱导GSK3β磷酸化和失活的瞬时增加，随后是β-catenin的核积累，这可能导致神经保护基因的上调。我们的结果表明，GSK3β是神经保护的新靶标，因此，我们证实了这两种GSK3β抑制剂N-（3-氯-4-甲基苯基）-5-（4-硝基苯基）-1,3,4-恶二唑-2-胺（TC-G 24）和LiCl是OGD中的神经保护剂，也可用作PostC剂。