One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death

One hour of pilocarpine-induced status epilepticus is sufficient to develop chronic epilepsy in mice, and is associated with mossy fiber sprouting but not neuronal death
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毛果芸香碱诱导的癫痫持续状态一小时足以使小鼠发展为慢性癫痫,并且与苔藓纤维发芽有关,但与神经元死亡无关

DOI:
10.1007/s12264-013-1310-6
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发表时间:
2013-06-01
影响因子:
5.6
通讯作者:
Zeng, Ling-Hui
Zeng, Ling-Hui
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Ling-Lin;Feng, Hang-Feng;Zeng, Ling-Hui

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确定导致随后自发发作(即癫痫)发展的癫痫持续状态(SE)的最短持续时间非常重要,因为它为癫痫干预和癫痫预防提供了一个关键的时间窗口。在本研究中,雄性ICR(印迹控制区)小鼠被注射匹罗卡品以诱导急性癫痫发作。在癫痫发作后10min、30min、1h、2 h和4h用安定终止Se。SE 1、2、4h组均可出现自发性发作,发作频率随SE时间延长而增加。Morris水迷宫实验显示,SE 1、2、4h组大鼠逃避潜伏期明显延长,目标象限穿越次数明显减少。在这些组中观察到了粗壮的苔藓纤维发芽,但在10或30分钟组中没有观察到。而荧光Jade B染色仅在SE后4h出现明显的细胞死亡。自发性癫痫的发生率和频率与TIMM评分(P=0.004)和逃避潜伏期(P=0.004)相关。这些数据表明,SE超过1小时会导致自发性运动性癫痫发作和记忆障碍,自发性癫痫发作可能与粗壮的苔藓纤维发芽有关,但与神经元死亡无关。
Determining the minimal duration of status epilepticus (SE) that leads to the development of subsequent spontaneous seizures (i.e., epilepsy) is important, because it provides a critical time-window for seizure intervention and epilepsy prevention. In the present study, male ICR (Imprinting Control Region) mice were injected with pilocarpine to induce acute seizures. SE was terminated by diazepam at 10 min, 30 min, 1 h, 2 h and 4 h after seizure onset. Spontaneous seizures occurred in the 1, 2 and 4 h SE groups, and the seizure frequency increased with the prolongation of SE. Similarly, the Morris water maze revealed that the escape latency was significantly increased and the number of target quadrant crossings was markedly decreased in the 1, 2 and 4 h SE groups. Robust mossy fiber sprouting was observed in these groups, but not in the 10 or 30 min group. In contrast, Fluoro-Jade B staining revealed significant cell death only in the 4 h SE group. The incidence and frequency of spontaneous seizures were correlated with Timm score (P= 0.004) and escape latency (P= 0.004). These data suggest that SE longer than one hour results in spontaneous motor seizures and memory deficits, and spontaneous seizures are likely associated with robust mossy fiber sprouting but not neuronal death.