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抗癫痫药物对Dravet综合征小鼠模型背景振荡的急性影响。

Acute effect of antiseizure drugs on background oscillations in Dravet syndrome mouse model.

作者信息

Quinn Shir, Brusel Marina, Ovadia Mor, Rubinstein Moran

机构信息

Goldschleger Eye Research Institute, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

出版信息

Front Pharmacol. 2023 Mar 20;14:1118216. doi: 10.3389/fphar.2023.1118216. eCollection 2023.

Abstract

Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, ), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.

摘要

德雷维特综合征(Dravet综合征)是一种罕见且严重的发育性癫痫性脑病。用于Dravet综合征患者的抗癫痫药物(ASMs)包括丙戊酸(VA)或氯巴占(CLB),可联合或不联合司替戊醇(STP)使用,而像卡马西平(CBZ)或拉莫三嗪(LTG)这样的钠通道阻滞剂则禁用。除了对癫痫表型有影响外,抗癫痫药物还被证明可改变背景神经元活动的特性。然而,对于Dravet综合征中这些背景特性的改变知之甚少。在这里,我们利用Dravet小鼠(DS小鼠),测试了几种抗癫痫药物对背景脑电图(ECoG)活动和发作间期棘波频率的急性影响。与野生型小鼠相比,DS小鼠的背景ECoG活动功率较低且相位相干性降低,所测试的任何一种抗癫痫药物都无法纠正这一情况。然而,急性给予Dravet综合征推荐药物VA、CLB或CLB + STP组合,在大多数小鼠中导致发作间期棘波频率降低,同时β频段的相对贡献增加。相反,CBZ和LTG增加了发作间期棘波的频率,对背景频谱特性没有影响。此外,我们发现发作间期棘波频率的降低、药物对背景活动功率的诱导效应以及向更高频段的频谱偏移之间存在相关性。总之,这些数据对所选抗癫痫药物对背景神经元振荡特性的影响进行了全面分析,并突出了它们对癫痫和背景活动的影响之间可能存在的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1df/10067575/6c52c375d738/fphar-14-1118216-g001.jpg

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