Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes
Implications of antiinflammatory properties of the anticonvulsant drug levetiracetam in astrocytes
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DOI：
10.1002/jnr.21639
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Faustmann, Pedro M.
中科院分区：
文献类型：
--
作者：
Haghikia, Aiden;Ladage, Kerstin;Faustmann, Pedro M.
越来越多的证据表明癫痫活动伴随着炎症过程。在本研究中，我们评估了左乙拉西坦（开普拉），一种具有决定性抗癫痫特征的抗惊厥药物，关于其假定的抗癫痫潜力的作用。我们以前建立了一个体外细胞培养模型，以模拟炎症条件：原代培养的新生大鼠星形胶质细胞与30%（M30）的小胶质细胞共培养。或者，将含有5%小胶质细胞（M5）的共培养物与促炎介质、细胞因子白细胞介素-1 β（IL-1 β）和脂多糖（LPS）（免疫系统的有效细菌激活剂）一起孵育。对于M30共培养物，我们观察到连接蛋白43（Cx43），主要的间隙连接蛋白的表达减少。在用IL-1 β和LPS处理的M30共培养物以及M5共培养物中监测受损的功能性染料偶联和去极化膜静息电位（MRP）。我们可以表明，Cx43的表达，耦合特性，和膜静息电位，我们专注于我们的炎症共培养模型下，左乙拉西坦（Keppra）治疗正常化到非炎症水平。累积起来，我们的研究结果提供了左乙拉西坦在癫痫发作治疗中的抗癫痫特性的证据。(c)2008 Wiley-Liss，Inc.
There is accumulating evidence that epileptic activity is accompanied by inflammatory processes. In the present study, we evaluated the effect of levetiracetam (Keppra), an anticonvulsant drug with decisive antiepileptic features, with regard to its putative antiinflammatory potential. We previously established an in vitro cell culture model to mimic inflammatory conditions: Primary astrocytic cultures of newborn rats were cocultured with 30% (M30) microglial cells. Alternatively, co-cultures containing 5% microglia (M5) were incubated with the proinflammatory mediator, the cytokine interleukin-1 beta (IL-1 beta), and lipopolysaccharide (LPS), a potent bacterial activator of the immune system. For the M30 cocultures, we observed reduced expression of connexin 43 (Cx43), the predominant gap junction protein. Impaired functional dye coupling and depolarized membrane resting potential (MRP) were monitored in M30 cocultures as well as in M5 cocultures treated with IL-1 beta and LPS. We could show that the Cx43 expression, the coupling property, and the membrane resting potential on which we focused our inflammatory coculture model were normalized to noninflammatory level under treatment with levetiracetam (Keppra). Cumulatively, our results provide evidence for antiinflammatory properties of levetiracetam in seizure treatment. (c) 2008 Wiley-Liss, Inc.