Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: An ontogenic study
Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling: An ontogenic study
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DOI：
10.1111/j.1528-1167.2008.01674.x
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发表时间：
2008-10-01
期刊：
影响因子：
5.6
通讯作者：
Sankar, Raman
中科院分区：
文献类型：
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作者：
Mazarati, Andrey;Wu, Jim;Sankar, Raman
目的：目的：探讨瑞替加宾（retigabine，RTG）在不同发育阶段快速点燃癫痫模型中的抗癫痫作用。方法：实验采用出生后14天（P14）、21和35天的雄性Wistar大鼠。在立体定向植入海马刺激电极和记录电极后，研究了RTG对基础后放电（AD）特性的影响。接下来，对动物进行快速点燃（60个10秒串，每5分钟递送一次双极20 Hz方波脉冲）。在RTG和溶剂处理的大鼠之间比较癫痫发作的进展（点燃获得）和点燃后对测试刺激的反应（保持）。此外，RTG对癫痫发作的严重程度在以前点燃的动物examined.Results的影响：当给药intraperitoneally的剂量，只引起轻度，或没有运动缺陷，RTG显着抑制脑兴奋性，明显的AD阈值的增加和AD持续时间的缩短。在点燃过程中，RTG延迟了P14大鼠局灶性癫痫发作的发展，并阻止了所有三个年龄的边缘系统癫痫发作的发生。在P14和P21，RTG预处理阻止了点燃诱导的癫痫发作易感性增强的建立，但在P35则不然。给点燃的动物施用RTG可降低由测试刺激诱导的癫痫发作的严重程度。结论：RTG在快速点燃模型中具有抗癫痫和抗癫痫的作用。这些影响在新生儿后期、幼儿期和青少年发育阶段都很明显。
Purpose: To examine antiepileptogenic and antiictogenic potential of retigabine (RTG) under conditions of rapid kindling epileptogenesis during different stages of development.Methods: The experiments were performed in postnatal day 14 (P14), P21, and P35 male Wistar rats. After stereotaxic implantation of hippocampal stimulating and recording electrodes, the effects of RTG on baseline afterdischarge (AD) properties were studied. Next, the animals underwent rapid kindling (sixty 10 s trains, bipolar 20 Hz square wave pulses delivered every 5 min). The progression of seizures (kindling acquisition), and responses to test stimulations after kindling (retention) were compared between RTG and vehicle-treated rats. Additionally, the effects of RTG on the severity of seizures in previously kindled animals were examined.Results: When administered intraperitoneally in doses that induced only mild, or no motor deficits, RTG significantly dampened brain excitability, evident as the increase of AD threshold and shortening of AD duration. During kindling, RTG delayed the development of focal seizures in P 14 rats, and prevented the occurrence of full limbic seizures at all three ages. At P14 and P21, but not at P35, pretreatment with RTG prevented the establishment of kindling-induced enhanced seizure susceptibility. Administration of RTG to kindled animals decreased the severity of seizures induced by test stimulation. The effect was most prominentat P14.Discussion: RTG exerted both antiepileptogenic and antiictogenic effects under conditions of rapid kindling model. These effects were apparent during postneonatal, early childhood, and adolescent stages of development.