Confounding effect of EEG implantation surgery: Inadequacy of surgical control in a two hit model of temporal lobe epilepsy
Confounding effect of EEG implantation surgery: Inadequacy of surgical control in a two hit model of temporal lobe epilepsy
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DOI：
10.1016/j.neulet.2016.04.033
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发表时间：
2016-05-27
影响因子：
2.5
通讯作者：
Koh, Sookyong
中科院分区：
文献类型：
--
作者：
Balzekas, Irena;Hernandez, Jose;Koh, Sookyong
在癫痫的啮齿动物模型中，脑电植入手术是评估脑电癫痫发作的基本手段。植入脑电电极的炎症后果及其对癫痫敏感性的影响尚不清楚。我们评估了电极植入在C57BL/6小鼠两次致痫模型中的作用，其中包括P14时的短暂、反复的热性惊厥(FS)和P28时的红藻氨酸诱发癫痫(KA-SZ)。在KA-SZ期间，测量首次心电图和行为发作的潜伏期、发作严重程度和KA剂量敏感性。无论早期癫痫发作经历如何，在P25接受硬膜下螺丝电极植入以进行P28脑电监测的小鼠比假小鼠的癫痫发作潜伏期显著缩短。电极植入小鼠对低剂量KA敏感，当KA剂量大于10 mg/kg时死亡率较高。然后，我们直接比较了小胶质细胞表达绿色荧光蛋白(GFP)的CX3CR1(GFP/+)转基因C57BL/6小鼠癫痫发作初期的电极植入和KA-SZ，以确定小胶质细胞的手术相关激活是否与二次打击模型中电极植入小鼠癫痫易感性的增加有关。癫痫发作前，植入电极的小鼠和对照组之间，用面积百分比GFP信号和GFP阳性细胞计数所显示的海马区小胶质细胞的激活是无法区分的，但在癫痫发作后，植入电极的小鼠显著更强。电极植入对随后癫痫发作的炎症反应具有混杂的启动效应。(C)2016年提交人。爱思唯尔爱尔兰有限公司出版。
In rodent models of epilepsy, EEG implantation surgery is an essential modality to evaluate electrographic seizures. The inflammatory consequences of EEG electrode-implantation and their resultant effects on seizure susceptibility are unclear. We evaluated electrode-implantation in a two-hit model of epileptogenesis in C57BL/6 mice that included brief, recurrent febrile seizures (FS) at P14 and kainic acid induced seizures (KA-SZ) at P28. During KA-SZ, latencies to first electrographic and behavioral seizures, seizure severity, and KA dose sensitivity were measured. Mice that received subdural screw electrode implants at P25 for EEG monitoring at P28 had significantly shorter latencies to seizures than sham mice, regardless of early life seizure experience. Electrode-implanted mice were sensitive to low dose KA as shown by high mortality rate at KA doses above 10 mg/kg. We then directly compared electrode-implantation and KA-SZ in seizure naive CX3CR1(GFP/+) transgenic C57BL/6 mice, wherein microglia express green fluorescent protein (GFP), to determine if microglia activation related to surgery was associated with the increased seizure susceptibility in electrode-implanted mice from the two-hit model. Hippocampal microglia activation, as demonstrated by percent area GFP signal and GFP positive cell counts, prior to seizures was indistinguishable between electrode-implanted mice and controls, but was significantly greater in electrode-implanted mice following seizures. Electrode-implantation had a confounding priming effect on the inflammatory response to subsequent seizures. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.