Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology.
Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology.
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DOI：
10.3389/fneur.2017.00588
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发表时间：
2017
影响因子：
3.4
通讯作者：
Dedeurwaerdere S
中科院分区：
文献类型：
--
作者：
Bertoglio D;Amhaoul H;Van Eetveldt A;Houbrechts R;Van De Vijver S;Ali I;Dedeurwaerdere S
癫痫模型的目的是以一致和前瞻性的方式研究疾病的发生和治疗干预。kainic酸诱导的癫痫持续状态（KASE）大鼠模型是颞叶癫痫（TLE）的一种广泛应用且验证良好的模型。由于我们注意到模型在实验室之间的显著差异可能与所使用的大鼠品系有关，我们旨在描述该模型的两种变体，它们具有不同的癫痫表型和神经病理学。此外，我们评估了两种不同的方案来诱导癫痫持续状态（SE）。Wistar Han （Charles River，法国）和Sprague-Dawley （Harlan，荷兰）大鼠采用Hellier kainic acid （KA）和改良的注射方案进行KASE。分别于SE发作后1周（亚急性期）和12周（慢性期）处死，用视像脑电图（vEEG）观察SE发作时间和潜伏期。在se后12周，用vEEG监测癫痫发作。评估神经元损失（神经元核）、小胶质细胞活化（OX-42和转运蛋白）和神经退行性变（Fluorojade C）。首先，与SD/H动物相比，Hellier方案导致WH/CR大鼠的死亡率非常高。修改后的方案导致WH/CR和SD/H大鼠的SE严重程度相似，但有效提高了生存率。SD/H潜伏期（中位8.3天）明显短于WH/CR潜伏期（中位15.4天）（p < 0.0001）。在慢性期，SD/H大鼠比WH/CR大鼠每天发作次数更多（p < 0.01）。然而，与SD/H大鼠相比，WH/CR大鼠的神经元变性和细胞丢失总体上更为广泛；在se后1周，两株大鼠的小胶质细胞活性相似，但在se后12周，WH/CR大鼠的小胶质细胞活性更高。这些神经病理差异可能更多地与KA在两种大鼠品系中不同的神经毒性作用有关，而不是癫痫发作负担本身的结果。疾病进展和发作结果的差异，加上组织病理学上的差异，进一步证实了KASE大鼠TLE模型存在品系差异。
The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden itself. The divergences in disease progression and seizure outcome, in addition to the histopathological dissimilarities, further substantiate the existence of strain differences for the KASE rat model of TLE.
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影响因子：
15.1
作者：
Bertoglio, Daniele;Verhaeghe, Jeroen;Dedeurwaerdere, Stefanie
通讯作者：
Dedeurwaerdere, Stefanie
DOI：
10.1016/j.nurt.2010.07.002
发表时间：
2010-10
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Loane DJ;Byrnes KR
通讯作者：
Byrnes KR
影响因子：
4.7
作者：
Drexel M;Preidt AP;Sperk G
通讯作者：
Sperk G
影响因子：
6.1
作者：
Amhaoul, Halima;Hamaide, Julie;Dedeurwaerdere, Stefanie
通讯作者：
Dedeurwaerdere, Stefanie
影响因子：
5.7
作者：
Dedeurwaerdere, S.;Fang, K.;O'Brien, T. J.
通讯作者：
O'Brien, T. J.