Chronic demyelination-induced seizures.
Chronic demyelination-induced seizures.
复制标题
DOI：
10.1016/j.neuroscience.2017.01.035
复制
发表时间：
2017-03-27
期刊：
影响因子：
3.3
通讯作者：
Tiwari-Woodruff SK
中科院分区：
文献类型：
--
作者：
Lapato AS;Szu JI;Hasselmann JPC;Khalaj AJ;Binder DK;Tiwari-Woodruff SK
多发性硬化症（MS）患者发生癫痫的可能性是其他人群的三到六倍。癫痫发作在早期发作或疾病进展形式的患者中更常见，并迅速进展为残疾和死亡。在MS癫痫患者中已经发现了灰质萎缩、海马病变、中间神经元丢失和前皮质病变负荷升高;然而，旨在阐明MS癫痫发生的病理生理过程的转化研究有限。在这里，我们报告了铜唑酮介导的慢性脱髓鞘（9-12周）小鼠表现出明显的脑电图（EEG）变化和明显的癫痫发作活动的证据。随后，组织病理学相关性进行了探讨，通过免疫组织化学，揭示广泛的脱髓鞘，海马CA 1区的小白蛋白抑制性中间神经元的损失，广泛的神经胶质增生和星形胶质细胞水通道蛋白-4表达的变化。我们的研究结果表明，慢性脱髓鞘小鼠是一个有价值的模型，我们可以开始了解脱髓鞘诱导癫痫发作的机制。
Multiple sclerosis (MS) patients are three to six times more likely to develop epilepsy compared to the rest of the population. Seizures are more common in patients with early onset or progressive forms of the disease and prognosticate rapid progression to disability and death. Grey matter atrophy, hippocampal lesions, interneuron loss, and elevated juxtacortical lesion burden have been identified in MS patients with seizures; however, translational studies aimed at elucidating the pathophysiological processes underlying MS epileptogenesis are limited. Here, we report that cuprizone-mediated chronically demyelinated (9-12 weeks) mice exhibit marked changes in electroencephalography (EEG) and evidence of overt seizure activity in mice. Subsequently, histopathological correlates were probed by immunohistochemistry, revealing extensive demyelination, loss of parvalbumin inhibitory interneurons in the hippocampus CA1 subregion, widespread gliosis and changes to astrocytic aquaporin-4 expression. Our results suggest that chronically demyelinated mice are a valuable model with which we may begin to understand the mechanisms underlying demyelination-induced seizures.