Twele Friederike, Töllner Kathrin, Bankstahl Marion, Löscher Wolfgang
Department of Pharmacology, Toxicology, and PharmacyUniversity of Veterinary Medicine HannoverHannoverGermany.
Center for Systems Neuroscience Hannover Germany.
Epilepsia Open. 2016 Jul 27;1(1-2):45-60. doi: 10.1002/epi4.2. eCollection 2016 Sep.
Mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis is a predominant form of acquired epilepsy, characterized by recurrent simple and complex partial seizures that are often resistant to treatment. Mice developing spontaneous recurrent nonconvulsive and convulsive seizures after intrahippocampal injection of the excitotoxic glutamate agonist kainate are thought to represent a valuable model of mesial TLE. Epileptic electroencephalogram (EEG) activity recorded in this model from the kainate focus in the ipsilateral hippocampus is resistant to antiseizure drugs such as carbamazepine (CBZ). We compared the efficacy of CBZ in this model in two different mouse strains (FVB/N and NMRI). Furthermore, we evaluated whether changes in the definition of electrographic seizures affect the antiseizure efficacy of CBZ.
As in previous studies, two types of epileptic EEG activity were defined: high-voltage sharp waves (HVSWs) and hippocampal paroxysmal discharges (HPDs). The characteristics of these paroxysmal EEG events in epileptic mice were compared with EEG criteria for nonconvulsive seizures in patients. For HVSWs, different spike frequencies, interevent intervals, and amplitudes were used as inclusion and exclusion criteria. In addition to CBZ, some experiments were performed with diazepam (DZP) and phenobarbital (PB).
Female epileptic FVB/N mice predominantly exhibited frequent HVSWs, but only infrequent HPDs or secondarily generalized convulsive seizures. Slight changes in HVSW definition determined whether they were resistant or responsive to CBZ. Male NMRI mice exhibited both HVSWs and HPDs. HVSWs were more resistant than HPDs to suppression by CBZ. Both types of epileptic EEG activity were rapidly suppressed by DZP and PB.
The data demonstrate that focal electrographic seizures in the intrahippocampal kainate mouse model are less resistant than previously thought. Both mouse strain and the criteria chosen for definition of EEG seizures determine whether such seizures are drug-resistant or -responsive.
伴有海马硬化的内侧颞叶癫痫（TLE）是获得性癫痫的主要形式，其特征为反复发作的简单和复杂部分性发作，且常对治疗耐药。海马内注射兴奋性毒性谷氨酸激动剂海藻酸后出现自发性反复非惊厥性和惊厥性发作的小鼠被认为是内侧TLE的一种有价值的模型。在此模型中，从同侧海马的海藻酸病灶记录到的癫痫性脑电图（EEG）活动对卡马西平（CBZ）等抗癫痫药物耐药。我们比较了CBZ在该模型中对两种不同小鼠品系（FVB/N和NMRI）的疗效。此外，我们评估了脑电图发作定义的改变是否会影响CBZ的抗癫痫疗效。
与先前研究一样，定义了两种类型的癫痫性EEG活动：高压棘波（HVSW）和海马阵发性放电（HPD）。将癫痫小鼠中这些阵发性EEG事件的特征与患者非惊厥性发作的EEG标准进行比较。对于HVSW，使用不同的棘波频率、事件间隔和幅度作为纳入和排除标准。除了CBZ，还使用地西泮（DZP）和苯巴比妥（PB）进行了一些实验。
雌性癫痫FVB/N小鼠主要表现为频繁的HVSW，但很少出现HPD或继发性全身性惊厥发作。HVSW定义的轻微变化决定了它们对CBZ耐药还是敏感。雄性NMRI小鼠同时表现出HVSW和HPD。HVSW比HPD更难被CBZ抑制。两种类型的癫痫性EEG活动都被DZP和PB迅速抑制。
数据表明，海马内注射海藻酸小鼠模型中的局灶性脑电图发作的耐药性比先前认为的要低。小鼠品系和用于定义EEG发作的标准都决定了这些发作是耐药还是敏感。
