Fan Jingjing, Shan Wei, Yang Huajun, Zhu Fei, Liu Xiao, Wang Qun
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
National Center for Clinical Medicine of Neurological Diseases, Beijing, China.
Front Mol Neurosci. 2020 Jan 15;12:323. doi: 10.3389/fnmol.2019.00323. eCollection 2019.
To clarify the different regional brain electroencephalogram (EEG) activities and biochemical responses in seizure and epilepsy models, we assessed the EEG and c-Fos immunolabeling characteristics in a lithium-pilocarpine-induced status epilepticus (SE) model and pentylenetetrazol (PTZ)-induced seizure model. The regional brain activities were evaluated by EEG and c-Fos immunolabeling. ZnT3 immunostaining was performed to observe hippocampal mossy fiber sprouting (MFS) within 7 days after the induction of SE in the lithium-pilocarpine model. The EEG recordings showed distinctive features of activation in different brain areas. With the aggravation of the behavioral manifestations of the seizures, the frequency and amplitude of the discharges on EEG gradually increased. SE was eventually induced and sustained. The labeling of c-Fos was enhanced in the cortex and hippocampal CA1, CA3, and dentate gyrus (DG); however, compared to the PTZ-induced seizure model, c-Fos staining could only be observed in the striatum and thalamus in the lithium-pilocarpine-induced epilepsy model. In each brain region, prominent c-Fos labeling was observed 2 h and 4 h after the induction of SE or seizures and diminished at 24 h. During the lithium-pilocarpine-induced chronic epilepsy phase after SE induction, MFS was observed 7 days after SE and was accompanied by the dynamic evolution of epileptic EEG activities. These findings validated the lithium-pilocarpine-induced SE model as an epilepsy model with a specific spatial-temporal profile of neural activation. The EEG characteristics and c-Fos expression patterns differ from those presented in a previous study using a PTZ-induced seizure model. Hippocampal mossy fiber spouting might be associated with spontaneous seizures during the chronic phase and can be detected at least within 1 week by ZnT3 staining after stimulation.
为了阐明癫痫发作和癫痫模型中不同脑区的脑电图(EEG)活动及生化反应,我们评估了锂-匹罗卡品诱导的癫痫持续状态(SE)模型和戊四氮(PTZ)诱导的癫痫发作模型中的EEG及c-Fos免疫标记特征。通过EEG和c-Fos免疫标记评估脑区活动。在锂-匹罗卡品模型中,于SE诱导后7天内进行锌转运体3(ZnT3)免疫染色以观察海马苔藓纤维出芽(MFS)。EEG记录显示不同脑区有独特的激活特征。随着癫痫发作行为表现的加重,EEG上放电的频率和幅度逐渐增加。最终诱导并维持了SE。c-Fos在皮质、海马CA1、CA3和齿状回(DG)中的标记增强;然而,与PTZ诱导的癫痫发作模型相比,在锂-匹罗卡品诱导的癫痫模型中,仅在纹状体和丘脑中观察到c-Fos染色。在每个脑区,SE或癫痫发作诱导后2小时和4小时观察到明显的c-Fos标记,24小时时减弱。在锂-匹罗卡品诱导的SE后的慢性癫痫阶段,SE后7天观察到MFS,并伴有癫痫性EEG活动的动态演变。这些发现证实锂-匹罗卡品诱导的SE模型是一种具有特定神经激活时空特征的癫痫模型。EEG特征和c-Fos表达模式与先前使用PTZ诱导的癫痫发作模型的研究结果不同。海马苔藓纤维出芽可能与慢性期的自发性癫痫发作有关,并且在刺激后至少1周内可通过ZnT3染色检测到。