The effect of propofol postconditioning on the expression of K+-Cl--co-transporter 2 in GABAergic inhibitory interneurons of acute ischemia/reperfusion injury rats
The effect of propofol postconditioning on the expression of K+-Cl--co-transporter 2 in GABAergic inhibitory interneurons of acute ischemia/reperfusion injury rats
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DOI：
10.1016/j.brainres.2014.11.036
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发表时间：
2015-02
期刊：
影响因子：
2.9
通讯作者：
Hongbai Wang;Shuying Liu;Haiyun Wang;Guolin Wang;Ai Zhu
中科院分区：
文献类型：
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作者：
Hongbai Wang;Shuying Liu;Haiyun Wang;Guolin Wang;Ai Zhu
我们的前期研究表明，异丙酚后处理可增强磷脂酰肌醇-3-激酶（PI 3 K）的活性，抑制α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体GluR 2亚基的内化，从而对脑缺血/再灌注（I/R）损伤起到神经保护作用。在中枢神经系统的抑制系统中，K ~+-Cl ~-共转运蛋白2（KCC 2）作为Cl ~-的挤出器，在成熟中枢神经元的γ-氨基丁酸（GABA）抑制效应中起着关键作用。然而，异丙酚后处理对GABA能中间神经元KCC 2表达的影响尚不清楚。因此，在这篇文章中，我们描述了KCC 2在成年大鼠同侧海马CA 1区GABA能中间神经元中的作用以及丙泊酚后处理对该区域的影响。丙泊酚后处理（20 mg/kg/h，2 h）可改善大鼠缺血再灌注后24 h的神经行为能力，增加存活神经元数量，并上调海马CA 1区表达GAD 67的GABA能中间神经元KCC 2的表达。相反，当大鼠注射KCC 2拮抗剂[（二氢茚基）氧基]链烷酸（DIOA）时，丙泊酚后处理诱导的神经保护作用被逆转。我们的研究表明，异丙酚后处理增加抑制性GABA能中间神经元KCC 2的表达，从而对脑I/R损伤大鼠提供急性神经保护。
It has been shown in our previous study that propofol postconditioning enhanced the activity of phosphatidylinositol-3-kinase (PI3K) and prevented the internalization of GluR2 subunit of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, thus provided neuroprotection in cerebral ischemia/reperfusion (I/R) injury. Regarding inhibitory system in CNS, K+-Cl--co-transporter 2 (KCC2), a Cl-extruder, plays a critical role in gamma-aminobutyric acid (GABA) inhibitory effect in mature central neurons. However, the effect of propofol postconditioning on the expression of KCC2 in GABAergic interneurons is unclear. Therefore, in this article we describe the role of KCC2 in GABAergic interneurons in the ipsilateral hippocampal CA1 region of adult rats and the effects of propofol postconditioning on this region. Herein we demonstrate that propofol postconditioning (20 mg/kg/h, 2 h) improved rats׳ neurobehavioral abilities, increased the number of survival neurons, and up-regulated neuronal KCC2 expression in glutamic acid decarboxylase 67 (GAD67) expressing GABAergic interneurons in hippocampal CA1 region at 24 h after I/R. In contrast, when rats were injected with the KCC2 antagonist, [(dihydroindenyl)oxy] alkanoic acid (DIOA), the neuroprotective effects induced by propofol postconditioning were reversed. Our study indicated that propofol postconditioning increased the expression of KCC2 in inhibitory GABAergic interneurons, thus providing acute neuroprotection to rats who had undergone cerebral I/R injury.