首页> 美国卫生研究院文献>The Journal of Neuroscience >Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission
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Eight Flurothyl-Induced Generalized Seizures Lead to the Rapid Evolution of Spontaneous Seizures in Mice: A Model of Epileptogenesis with Seizure Remission

机译:八氟诱导的全身性癫痫发作导致小鼠自发性癫痫的快速发展:癫痫发作与癫痫发作缓解的模型。

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摘要

The occurrence of recurrent, unprovoked seizures is the hallmark of human epilepsy. Currently, only two-thirds of this patient population has adequate seizure control. New epilepsy models provide the potential for not only understanding the development of spontaneous seizures, but also for testing new strategies to treat this disorder. Here, we characterize a primary generalized seizure model of epilepsy following repeated exposure to the GABAA receptor antagonist, flurothyl, in which mice develop spontaneous seizures that remit within 1 month. In this model, we expose C57BL/6J mice to flurothyl until they experience a generalized seizure. Each of these generalized seizures typically lasts <30 s. We induce one seizure per day for 8 d followed by 24 h video-electroencephalographic recordings. Within 1 d following the last of eight flurothyl-induced seizures, ∼50% of mice have spontaneous seizures. Ninety-five percent of mice tested have seizures within the first week of the recording period. Of the spontaneous seizures recorded, the majority are generalized clonic seizures, with the remaining 7–12% comprising generalized clonic seizures that transition into brainstem seizures. Over the course of an 8 week recording period, spontaneous seizure episodes remit after ∼4 weeks. Overall, the repeated flurothyl paradigm is a model of epileptogenesis with spontaneous seizures that remit. This model provides an additional tool in our armamentarium for understanding the mechanisms underlying epileptogenesis and may provide insights into why spontaneous seizures remit without anticonvulsant treatment. Elucidating these processes could lead to the development of new epilepsy therapeutics.>SIGNIFICANCE STATEMENT Epilepsy is a chronic disorder characterized by the occurrence of recurrent, unprovoked seizures in which the individual seizure–ictal events are self-limiting. Remission of recurrent, unprovoked seizures can be achieved in two-thirds of cases by treatment with anticonvulsant medication, surgical resection, and/or nerve/brain electrode stimulation. However, there are examples in humans of epilepsy with recurrent, unprovoked seizures remitting without any intervention. While elucidating how recurrent, unprovoked seizures develop is critical for understanding epileptogenesis, an understanding of how and why recurrent, unprovoked seizures remit may further our understanding and treatment of epilepsy. Here, we describe a new model of recurrent, unprovoked spontaneous seizures in which the occurrence of spontaneous seizures naturally remits over time without any therapeutic intervention.
机译:反复发作,无故发作是人类癫痫的标志。目前,只有三分之二的患者能充分控制癫痫发作。新的癫痫模型不仅为了解自发性癫痫的发展提供了潜力,而且还为测试治疗这种疾病的新策略提供了潜力。在这里,我们表征重复暴露于GABAA受体拮抗剂氟尿嘧啶后的癫痫的主要广义癫痫发作模型,其中小鼠发展为自发性癫痫发作,并在1个月内缓解。在此模型中,我们将C57BL / 6J小鼠暴露于氟尿嘧啶中,直到它们遭受全身性癫痫发作。这些全身性癫痫发作通常持续30秒以下。我们每天诱发一次癫痫发作,持续8天,然后进行24小时视频脑电图记录。在八次氟尿嘧啶诱发的癫痫发作的最后一次之后的1 d内,约50%的小鼠具有自发性癫痫发作。在记录期的第一周内,有95%的受测小鼠有癫痫发作。在记录的自发性癫痫发作中,大多数是全身性阵挛性癫痫发作,其余7–12%包括转变为脑干性癫痫发作的全身性阵挛性癫痫发作。在8周的记录期内,约4周后会自发发作。总的来说,重复的氟乙基范例是癫痫发生的模型,具有自发性发作。该模型在我们的军备库中提供了一个额外的工具,用于了解癫痫发生的潜在机制,并可能提供有关为何不进行抗惊厥治疗即可自发发作的见解。阐明这些过程可能会导致新的癫痫治疗方法的发展。>意义声明。癫痫病是一种慢性疾病,其特征是反复发作,无缘无故的癫痫发作,其中个别的发作-发作事件是自限性的。通过使用抗惊厥药物,手术切除和/或神经/脑电极刺激治疗,可以在三分之二的病例中缓解复发性,无故的癫痫发作。但是,在癫痫病患者中,有一些例子是反复发作,无故发作而无需任何干预。尽管阐明了反复发作的,无缘无故的癫痫发作对于理解癫痫发生至关重要,但了解复发发作的,无缘无故的癫痫发作的缓解方式和原因可能会进一步加深我们对癫痫的理解和治疗。在这里,我们描述了一种复发性,无缘自发性癫痫发作的新模型,在这种模型中,自发性癫痫发作会随着时间的推移自然缓解,而无需任何治疗干预。

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