Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices.
Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices.
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DOI：
10.1038/s41598-017-12346-y
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发表时间：
2017-09-19
影响因子：
4.6
通讯作者：
Zhou N
中科院分区：
文献类型：
--
作者：
Lin CH;Hsu SP;Cheng TC;Huang CW;Chiang YC;Hsiao IH;Lee MH;Shen ML;Wu DC;Zhou N
癫痫和扩散性去极化（SD）都是发作性脑功能障碍，通常同时存在于同一个体中。在小鼠海马脑片的CA 1区锥体神经元中，SD的诱导诱发癫痫样活动，包括发作样爆发，这发生在SD的复极化阶段，以及随后产生的阵发性去极化移位（PDS），其特征在于具有覆盖棘波的轻度去极化平台。癫痫样活动持续时间与SD的恢复时间和去极化电位相关，而PD参数与SD参数无显著相关性。此外，我们系统地评估了多种抗癫痫药物（AEDs）对SD诱导的癫痫样活动的影响。在已知抑制电压门控钠通道的药物中，卡马西平、苯妥英、丙戊酸盐、拉莫三嗪和唑尼沙胺在诱导SD后20-25分钟内降低了PDS的频率和压倒性放电爆发。GABA摄取抑制剂噻加宾表现出中度影响，并部分限制SD后PDS的发生率。包括加巴喷丁、左乙拉西坦、乙琥胺、非氨酯和氨己烯酸在内的AED对SD诱导的癫痫活动无显著影响。综上所述，这些结果证明了抗癫痫药物对SD和相关癫痫样活动在细胞水平的影响。
Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD. Moreover, we systematically evaluated the effects of multiple anti-epileptic drugs (AEDs) on SD-induced epileptiform activity. Among the drugs that are known to inhibit voltage-gated sodium channels, carbamazepine, phenytoin, valproate, lamotrigine, and zonisamide reduced the frequency of PDSs and the overriding firing bursts in 20–25 min after the induction of SD. The GABA uptake inhibitor tiagabine exhibited moderate effects and partially limited the incidence of PDSs after SD. AEDs including gabapentin, levetiracetam, ethosuximide, felbamate, and vigabatrin, had no significant effect on SD-induced epileptic activity. Taken together, these results demonstrate the effects of AEDs on SD and the related epileptiform activity at the cellular level.
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影响因子：
11.2
作者：
COULTER, DA;HUGUENARD, JR;PRINCE, DA
通讯作者：
PRINCE, DA
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Ayata, Cenk
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通讯作者：
Woodruff, GN