Ben-Ari Yehezkel, Holmes Gregory L
Institute of Neurobiology of the Mediterranean Sea (INMED, INSERM and Université de la Méditerranée), Marseilles, France.
Lancet Neurol. 2006 Dec;5(12):1055-63. doi: 10.1016/S1474-4422(06)70626-3.
Infants and children are at a high risk for seizures compared with adults. Although most seizures in children are benign and result in no long-term consequences, increasing experimental animal data strongly suggest that frequent or prolonged seizures in the developing brain result in long-lasting sequelae. Such seizures may intervene with developmental programmes and lead to inadequate construction of cortical networks rather than induction of neuronal cell loss. As a consequence, the deleterious actions of seizures are strongly age dependent: seizures have different effects on immature or migrating neurons endowed with few synapses and more developed neurons that express hundreds of functional synapses. This differential effect is even more important in human beings and subhuman primates who have an extended brain development period. Seizures also beget seizures during maturation and result in a replay of development programmes, which suggests that epileptogenesis recapitulates ontogenesis. Therefore, to understand seizures and their consequences in the developing brain, it is essential to determine how neuronal activity modulates the main steps of cortical formation. In this Review, we present basic developmental principles obtained from animal studies and examine the long-lasting consequences of epilepsy.
与成年人相比，婴幼儿和儿童发生癫痫的风险更高。尽管儿童的大多数癫痫发作是良性的，不会导致长期后果，但越来越多的实验动物数据强烈表明，发育中的大脑频繁或长时间发作会导致长期后遗症。此类发作可能干扰发育程序，导致皮质网络构建不足，而非诱导神经元细胞死亡。因此，癫痫发作的有害作用在很大程度上取决于年龄：癫痫发作对突触较少的未成熟或迁移神经元与表达数百个功能性突触的发育更成熟的神经元有不同影响。这种差异效应在脑发育时期延长的人类和非人灵长类动物中更为重要。癫痫发作还会在成熟过程中引发癫痫发作，并导致发育程序重演，这表明癫痫发生重现了个体发生过程。因此，为了理解癫痫发作及其在发育中大脑的后果，确定神经元活动如何调节皮质形成的主要步骤至关重要。在本综述中，我们介绍了从动物研究中获得的基本发育原理，并探讨了癫痫的长期后果。
