Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, 3801 University Street, Montréal, Qc H3A 2B4, Canada.
Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, 3801 University Street, Montréal, Qc H3A 2B4, Canada.
Neuroscience. 2019 Nov 21;421:112-122. doi: 10.1016/j.neuroscience.2019.10.009. Epub 2019 Nov 6.
Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those seen in humans is reproduced in rodents by i.p. pilocarpine injection, and can be terminated by diazepam and ketamine treatment but only behaviourally, not electrographically. Little is known on the behavioral and EEG effects induced by a delayed administration of ketamine (25 mg/kg) after diazepam (10 mg/kg) or vice versa. Therefore, we analysed behavior and EEG activity recorded from the mouse hippocampal CA3 region before, during SE and after anticonvulsant treatments. In the first group (n = 4), diazepam was administered one hour before ketamine whereas in the second group (n = 4) ketamine was administered one hour before diazepam. The EEG SE did not disappear after each of the two treatments but progressed within 4 h to a pattern of interictal discharges. However, diazepam administration before ketamine significantly shortened the time of behavioral recovery compared to when ketamine was administered before diazepam (p < 0.05). The two protocols were also associated to distinct EEG changes in gamma and high frequency oscillations. In conclusion, although diazepam and ketamine are not effective in stopping EEG SE, diazepam administration one hour before ketamine shortens behavioral recovery in pilocarpine-treated mice.
癫痫持续状态（SE）是一种危及生命的疾病，需要立即进行护理以防止脑损伤。通过腹腔注射毛果芸香碱在啮齿动物中再现具有与人类相似的电生理和行为特征的 SE，可以用地西泮和氯胺酮治疗终止，但仅在行为上，而不在电生理上。对于地西泮（10mg/kg）后延迟给予氯胺酮（25mg/kg）或反之亦然，其引起的行为和 EEG 影响知之甚少。因此，我们分析了在抗惊厥治疗之前、期间和之后从小鼠海马 CA3 区记录的行为和 EEG 活动。在第一组（n=4）中，地西泮在氯胺酮前一小时给予，而在第二组（n=4）中，氯胺酮在地西泮前一小时给予。两种治疗后，EEG SE 并未消失，而是在 4 小时内进展为发作间放电模式。然而，与氯胺酮先于地西泮给予相比，地西泮先于氯胺酮给予显著缩短了行为恢复的时间（p<0.05）。这两种方案还与γ和高频振荡中的不同 EEG 变化相关。总之，尽管地西泮和氯胺酮不能有效停止 EEG SE，但地西泮在氯胺酮前一小时给予可缩短毛果芸香碱治疗小鼠的行为恢复时间。
