Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures.
Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures.
复制标题
对 C57BL/6J 小鼠重复低剂量红藻氨酸给药会产生颞叶癫痫病理，但很少发生自发性癫痫发作。
DOI：
10.1016/j.expneurol.2016.02.014
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发表时间：
2016
影响因子：
5.3
通讯作者：
Wilcox,KarenS
中科院分区：
文献类型：
--
作者：
Umpierre,AnthonyD;Bennett,IsaiahV;Nebeker,LismoreD;Newell,ThomasG;Tian,BruceB;Thomson,KyleE;White,HSteve;White,JohnA;Wilcox,KarenS
需要更有效的或与实验相关的方法来在遗传易处理的小鼠中建立获得性颞叶癫痫（TLE）模型。与育种和维持转基因、敲入或敲除品系相关的高成本对诱导效率和动物存活率具有很高的价值。在此，我们描述了我们的方法来模型获得性癫痫C57 BL/6 J小鼠使用重复，低剂量红藻氨酸（KA）管理模式。四种范式（i. p.）测试它们诱导癫痫持续状态（SE）、颞叶病理学和癫痫发展的能力。所有四个范例可靠地诱导行为和/或电描记SE在7天内没有死亡。研究的四个范例中的两个产生指示TLE病理学的特征，包括海马细胞死亡、广泛的星形胶质细胞增生和mGluR 5的星形胶质细胞表达，这是TLE模型中通常报告的特征。三个研究范式能够产生异常的电图功能，如发作间期在皮层尖峰。然而，只有一个范例，以前发表的其他人，产生自发复发性癫痫发作超过八周的时间。自发性癫痫发作罕见（N = 2/14），癫痫发作优先发生在SE期间癫痫发作次数较多的动物中。总的来说，重复的低剂量KA施用改善了系统性KA损伤的效率和病理相关性，但在本文所述的实验范例下不产生稳健的癫痫表型。
More efficient or translationally relevant approaches are needed to model acquired temporal lobe epilepsy (TLE) in genetically tractable mice. The high costs associated with breeding and maintaining transgenic, knock-in, or knock-out lines place a high value on the efficiency of induction and animal survivability. Herein, we describe our approaches to model acquired epilepsy in C57BL/6J mice using repeated, low-dose kainate (KA) administration paradigms. Four paradigms (i.p.) were tested for their ability to induce status epilepticus (SE), temporal lobe pathology, and the development of epilepsy. All four paradigms reliably induce behavioral and/or electrographic SE without mortality over a 7 d period. Two of the four paradigms investigated produce features indicative of TLE pathology, including hippocampal cell death, widespread astrogliosis, and astrocyte expression of mGluR5, a feature commonly reported in TLE models. Three of the investigated paradigms were able to produce aberrant electrographic features, such as interictal spiking in cortex. However, only one paradigm, previously published by others, produces spontaneous recurrent seizures over an eight week period. Presentation of spontaneous seizures is rare (N = 2/14), with epilepsy preferentially developing in animals having a high number of seizures during SE. Overall, repeated, low-dose KA administration improves the efficiency and pathological relevance of a systemic KA insult, but does not produce a robust epilepsy phenotype under the experimental paradigms described herein.