Augmented seizure susceptibility and hippocampal epileptogenesis in a translational mouse model of febrile status epilepticus.
Augmented seizure susceptibility and hippocampal epileptogenesis in a translational mouse model of febrile status epilepticus.
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在一个转化的小鼠发热性癫痫持续状态模型中增加的癫痫发作易感性和海马癫痫发生。
作者：
Chen KD;Hall AM;Garcia-Curran MM;Sanchez GA;Daglian J;Luo R;Baram TZ
儿童早期长期发热诱发的惊厥（发热性癫痫持续状态[FSE]）增加了以后癫痫的风险，但其潜在机制尚不完全清楚。大鼠实验性FSE（eFSE）成功地模拟了人类FSE，重现了受影响个体亚组中的癫痫发生。然而，强大的病毒和遗传工具，可能会提高对癫痫发生和相关合并症的机械见解，是更好地为小鼠开发。因此，我们的目的是确定是否可以在小鼠中产生eFSE，以及它是否引起了突触网络兴奋性的持久变化和自发性癫痫发作的发展。我们采用C57 BL/6 J雄性小鼠，最常用的转基因操作的菌株，并检查是否可以维持生命早期的eFSE，如果它导致海马网络的过度兴奋和癫痫。结果的措施包括脆弱性，随后管理的边缘惊厥红藻氨酸（KA）和自发性癫痫发作的发展。在第一个小鼠队列中，将成年幼稚和经历eFSE的小鼠暴露于KA。第二组对照和经历eFSE的年轻成年小鼠植入双侧海马电极，并使用连续视频脑电图（EEG）记录2至3个月，以检查自发性癫痫发作（癫痫发生）。诱导eFSE是可行的，并且eFSE增加了成年C57 BL/6 J小鼠对KA的易感性，从而减少了癫痫发作的潜伏期并增加了癫痫发作的严重程度。在24只长期记录的eFSE小鼠中，4只（16.5%）发生海马癫痫，潜伏期约为3个月，与偶然预期有显著差异（P = .04）。eFSE后的边缘癫痫是进行性的。eFSE在大多数C57 BL/6 J雄性小鼠中促进促癫痫网络变化，并在六分之一的队列中促进明显的“颞叶样”癫痫。因此，小鼠eFSE可以提供一个有用的工具，调查分子，细胞和电路的变化，在颞叶癫痫及其合并症的发展。
Prolonged fever-induced seizures (febrile status epilepticus [FSE]) during early childhood increase the risk for later epilepsy, but the underlying mechanisms are incompletely understood. Experimental FSE (eFSE) in rats successfully models human FSE, recapitulating the resulting epileptogenesis in a subset of affected individuals. However, the powerful viral and genetic tools that may enhance mechanistic insights into epileptogenesis and associated comorbidities, are better-developed for mice. Therefore, we aimed to determine if eFSE could be generated in mice and if it provoked enduring changes in hippocampal-network excitability and the development of spontaneous seizures. We employed C57BL/6J male mice, the strain used most commonly in transgenic manipulations, and examined if early life eFSE could be sustained and if it led to hyperexcitability of hippocampal networks and to epilepsy. Outcome measures included vulnerability to the subsequent administration of the limbic convulsant kainic acid (KA) and the development of spontaneous seizures. In the first mouse cohort, adult naive and eFSE-experiencing mice were exposed to KA. A second cohort of control and eFSE-experiencing young adult mice was implanted with bilateral hippocampal electrodes and recorded using continuous video–electroencephalography (EEG) for 2 to 3 months to examine for spontaneous seizures (epileptogenesis). Induction of eFSE was feasible and eFSE increased the susceptibility of adult C57BL/6J mice to KA, thereby reducing latency to seizure onset and increasing seizure severity. Of 24 chronically recorded eFSE mice, 4 (16.5%) developed hippocampal epilepsy with a latent period of ~3 months, significantly different from the expectation by chance (P = .04). The limbic epilepsy that followed eFSE was progressive. eFSE promotes pro-epileptogenic network changes in a majority of C57BL/6J male mice and frank “temporal lobe–like” epilepsy in one sixth of the cohort. Mouse eFSE may thus provide a useful tool for investigating molecular, cellular, and circuit changes during the development of temporal lobe epilepsy and its comorbidities.
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影响因子：
5.3
作者：
Dutton SBB;Dutt K;Papale LA;Helmers S;Goldin AL;Escayg A
通讯作者：
Escayg A
影响因子：
5.6
作者：
Curran MM;Haddad E;Patterson KP;Choy M;Dubé CM;Baram TZ;Obenaus A
通讯作者：
Obenaus A
影响因子：
3.6
作者：
Jobst, Barbara C.;Ben-Menachem, Elinor;Lado, Fred
通讯作者：
Lado, Fred
影响因子：
3.7
作者：
Jongbloets BC;van Gassen KL;Kan AA;Olde Engberink AH;de Wit M;Wolterink-Donselaar IG;Groot Koerkamp MJ;van Nieuwenhuizen O;Holstege FC;de Graan PN
通讯作者：
de Graan PN
影响因子：
11.2
作者：
Lewis, Darrell V.;Shinnar, Shlomo;Hesdorffer, Dale C.;Bagiella, Emilia;Bello, Jacqueline A.;Chan, Stephen;Xu, Yuan;MacFall, James;Gomes, William A.;Moshe, Solomon L.;Mathern, Gary W.;Pellock, John M.;Nordli, Douglas R., Jr.;Frank, L. Matthew;Provenzale, James;Shinnar, Ruth C.;Epstein, Leon G.;Masur, David;Litherland, Claire;Sun, Shumei
通讯作者：
Sun, Shumei