PTZ-induced seizures in mice require a revised Racine scale

PTZ-induced seizures in mice require a revised Racine scale
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DOI:
10.1016/j.yebeh.2019.02.029
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发表时间:
2019-06-01
影响因子:
2.6
通讯作者:
De Deyn, Peter Paul
De Deyn, Peter Paul
中科院分区:
医学3区
文献类型:
--
作者:
Van Erum, Jan;Van Dam, Debby;De Deyn, Peter Paul

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癫痫实验模型中的癫痫发作严重程度通常通过Racine量表进行评估,尽管使用的癫痫发作诱导方法与Racine在1972年的原始论文中使用的方法不同。在这种情况下,使用该量表并不总是合理的,因为一些癫痫发作行为与最初描述的行为有显著差异或根本不存在。相应地,常用于抗癫痫药物研究的戊四唑(PTZ)模型缺乏足够的评估工具来测量癫痫发作的严重程度。2009年,已经为大鼠设计了一个适应性的PTZ诱导癫痫发作强度量表。在这里,我们评估了单次PTZ注射后的脑电图(EEG)和行为参数,以确定该量表是否也适用于小鼠研究。我们发现,为大鼠设计的量表是相当稳健的,因此可以应用于小鼠癫痫发作严重程度的评分。然而,某些惊厥行为和EEG特征在物种之间是不同的。因此,我们设计了一个物种特异性量表,其中包括伴随的EEG特征旁边的行为表达,我们观察到,以建立一个用户友好的评分量表PTZ诱导的小鼠癫痫发作。为了评估适用性,我们在转基因小鼠模型的癫痫发作易感性研究中使用了该量表。我们证明了最大严重程度评分与新修订的Racine量表高度相关的管理剂量。因此,修订后的量表可以很好地区分不同类别的癫痫发作严重程度。(C)2019作者爱思唯尔公司出版
Seizure severity in experimental models of epilepsy is often evaluated by means of the Racine scale, in spite of the use of seizure induction methods that are different from those of the original paper by Racine in 1972. In such cases, the use of this scale is not always justified because some seizure behaviors are significantly different from those originally described or not present at all. Correspondingly, the pentylenetetrazole (PTZ) model, which is frequently used for antiepileptic drug research, lacked an adequate assessment tool to measure seizure severity. In 2009, an adapted intensity scale for PTZ-induced seizures was already designed for rats. Here, we evaluated electroencephalographic (EEG) and behavioral parameters after a single PTZ injection, to determine whether this scale is also suitable for use in mouse studies. We found that the scale designed for rats is quite robust and can thus be applied to score seizure severity in mice. Yet, certain convulsive behaviors and EEG characteristics were distinct between species. Therefore, a species-specific scale was designed, which included the concomitant EEG characteristic next to the behavioral expressions we observed, in order to establish a user-friendly scoring scale for PTZ-induced seizures in mice. To evaluate applicability, we utilized the scale in a seizure susceptibility study of a transgenic mouse model. We demonstrated that the maximum severity scores obtained with the newly revised Racine scale highly correlated with the administered dose. Hence, the revised scale differentiates well between different classes of seizure severity. (C) 2019 The Authors. Published by Elsevier Inc.