Interictal spikes, seizures and ictal cell death are not necessary for post-traumatic epileptogenesis in vitro.
Interictal spikes, seizures and ictal cell death are not necessary for post-traumatic epileptogenesis in vitro.
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DOI：
10.1016/j.nbd.2011.11.001
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发表时间：
2012-02
影响因子：
6.1
通讯作者：
Staley, Kevin J.
中科院分区：
文献类型：
--
作者：
Berdichevsky, Yevgeny;Dzhala, Volodymyr;Mail, Michelle;Staley, Kevin J.
临床研究表明，苯妥英可预防急性创伤后癫痫发作，但不能预防随后的创伤后癫痫。我们使用器官型海马切片培养作为严重创伤性脑损伤的模型来探索这一现象。海马切片培养长达8周，在此期间，急性和慢性电记录显示自发性癫痫样放电的特征演变，包括间歇尖峰，癫痫发作活动和癫痫持续状态。细胞死亡在切片后立即出现早期高峰，随后的二次高峰与癫痫样活动的高峰相吻合。用犬尿酸阻断谷氨酸能传递或用苯妥英消除癫痫持续状态，可消除神经元死亡的次峰。停用犬尿酸或苯妥英后，自发发作活动急剧增加。苯妥英的抗惊厥和神经保护作用在连续用药四周后失效。这些数据支持临床发现，即脑损伤后，抗惊厥药可以预防癫痫发作，但不能预防癫痫或抗惊厥药耐药性的发展。我们通过显示继发性神经元死亡与发作期活动相关而非发作期活动相关来扩展临床数据，并且在体外模型中阻断所有这三种脑损伤后遗症并不能阻止癫痫发生。
Clinical studies indicate that phenytoin prevents acute post-traumatic seizures but not subsequent post-traumatic epilepsy. We explored this phenomenon using organotypic hippocampal slice cultures as a model of severe traumatic brain injury. Hippocampal slices were cultured for up to eight weeks, during which acute and chronic electrical recordings revealed a characteristic evolution of spontaneous epileptiform discharges, including interictal spikes, seizure activity and electrical status epilepticus. Cell death exhibited an early peak immediately following slicing, and a later secondary peak that coincided with the peak of seizure-like activity. The secondary peak in neuronal death was abolished by either blockade of glutamatergic transmission with kynurenic acid or by elimination of ictal activity and status epilepticus with phenytoin. Withdrawal of kynurenic acid or phenytoin was followed by a sharp increase in spontaneous seizure activity. Phenytoin’s anticonvulsant and neuroprotective effects failed after four weeks of continuous administration. These data support the clinical findings that after brain injury, anticonvulsants prevent seizures but not epilepsy or the development of anticonvulsant resistance. We extend the clinical data by showing that secondary neuronal death is correlated with ictal but not interictal activity, and that blocking all three of these sequelae of brain injury does not prevent epileptogenesis in this in vitro model.
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DOI：
10.1073/pnas.92.16.7162
发表时间：
1995-08-01
影响因子：
11.1
作者：
BONFOCO, E;KRAINC, D;LIPTON, SA
通讯作者：
LIPTON, SA
影响因子：
3.7
作者：
Houweling, AR;Bazhenov, M;Sejnowski, TJ
通讯作者：
Sejnowski, TJ
DOI：
10.1093/jnen/59.8.641
发表时间：
2000-08-01
影响因子：
3.2
作者：
Graham, DI;McIntosh, TK;Nicoll, JAR
通讯作者：
Nicoll, JAR
影响因子：
5.6
作者：
Buckmaster, PS
通讯作者：
Buckmaster, PS
影响因子：
4.8
作者：
Berg, Anne T.
通讯作者：
Berg, Anne T.