Yavuz Melis, İyiköşker Pelin, Mutlu Nursima, Kiliçparlar Serra, Şalci Öykü Hazal, Dolu Gökçen, Kaymakçilar Elif Nur, Akkol Serdar, Onat Filiz
Department of Pharmacology, Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Istanbul, Türkiye.
Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Istanbul, Türkiye.
Front Neurol. 2023 Dec 11;14:1231736. doi: 10.3389/fneur.2023.1231736. eCollection 2023.
The genetic absence epilepsy rat from Strasbourg (GAERS) is a rat model for infantile absence epilepsy with spike-and-wave discharges (SWDs). This study aimed to investigate the potential of alpha 2A agonism to induce seizures during the pre-epileptic period in GAERS rats.
Stereotaxic surgery was performed on male pups and adult GAERS rats to implant recording electrodes in the frontoparietal cortices (right/left) under anesthesia (PN23-26). Following the recovery period, pup GAERS rats were subjected to electroencephalography (EEG) recordings for 2 h. Before the injections, pup epileptiform activity was examined using baseline EEG data. Dexmedetomidine was acutely administered at 0.6 mg/kg to pup GAERS rats 2-3 days after the surgery and once during the post-natal (PN) days 25-29. Epileptiform activities before injections triggered unilateral SWDs and induced sleep durations, and power spectral density was evaluated based on EEG traces.
The most prominent finding of this study is that unilateral SWD-like activities were induced in 47% of the animals with the intraperitoneal dexmedetomidine injection. The baseline EEGs of pup GAERS rats had no SWDs as expected since they are in the pre-epileptic period but showed low-amplitude non-rhythmic epileptiform activity. There was no difference in the duration of epileptiform activities between the basal EEG groups and DEX-injected unilateral SWD-like-exhibiting and non-SWD-like activities groups; however, the sleep duration of the unilateral SWD-like-exhibiting group was shorter. Power spectrum density (PSD) results revealed that the 1.75-Hz power in the left hemisphere peaks significantly higher than in the right.
As anticipated, pup GAERS rats in the pre-epileptic stage showed no SWDs. Nevertheless, they exhibited sporadic epileptiform activities. Specifically, dexmedetomidine induced SWD-like activities solely within the left hemisphere. These observations imply that absence seizures might originate unilaterally in the left cortex due to αAR agonism. Additional research is necessary to explore the precise cortical focal point of this activity.
斯特拉斯堡遗传性失神癫痫大鼠（GAERS）是一种伴有棘波-慢波放电（SWDs）的婴儿失神癫痫大鼠模型。本研究旨在探讨α2A激动剂在GAERS大鼠癫痫前期诱发癫痫发作的可能性。
对雄性幼崽和成年GAERS大鼠进行立体定向手术，在麻醉状态下（出生后第23 - 26天）将记录电极植入额顶叶皮质（右/左）。恢复期后，对幼崽GAERS大鼠进行2小时的脑电图（EEG）记录。在注射前，使用基线EEG数据检查幼崽癫痫样活动。在手术后2 - 3天以及出生后（PN）第25 - 29天，对幼崽GAERS大鼠急性给予右美托咪定，剂量为0.6 mg/kg。根据EEG记录评估注射前触发单侧SWDs的癫痫样活动、诱导睡眠时间以及功率谱密度。
本研究最显著的发现是，腹腔注射右美托咪定后，47%的动物诱导出单侧SWD样活动。幼崽GAERS大鼠的基线EEG由于处于癫痫前期，未出现SWDs，但显示出低振幅非节律性癫痫样活动。基础EEG组与注射右美托咪定后出现单侧SWD样活动和未出现SWD样活动的组之间，癫痫样活动持续时间无差异；然而，出现单侧SWD样活动组的睡眠时间较短。功率谱密度（PSD）结果显示，左半球1.75 Hz的功率峰值显著高于右半球。
正如预期的那样，处于癫痫前期的幼崽GAERS大鼠未出现SWDs。然而，它们表现出散发性癫痫样活动。具体而言，右美托咪定仅在左半球诱导出SWD样活动。这些观察结果表明，失神发作可能由于αAR激动作用而单侧起源于左皮质。需要进一步研究以探索这种活动的确切皮质焦点。
