Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany .
Epilepsia. 2012 Nov;53(11):1868-76. doi: 10.1111/j.1528-1167.2012.03716.x. Epub 2012 Oct 12.
For several decades, both in vitro and in vivo models of seizures and epilepsy have been employed to unravel the molecular and cellular mechanisms underlying the occurrence of spontaneous recurrent seizures (SRS)-the defining hallmark of the epileptic brain. However, despite great advances in our understanding of seizure genesis, investigators have yet to develop reliable biomarkers and surrogate markers of the epileptogenic process. Sadly, the pathogenic mechanisms that produce the epileptic condition, especially after precipitating events such as head trauma, inflammation, or prolonged febrile convulsions, are poorly understood. A major challenge has been the inherent complexity and heterogeneity of known epileptic syndromes and the differential genetic susceptibilities exhibited by patients at risk. Therefore, it is unlikely that there is only one fundamental pathophysiologic mechanism shared by all the epilepsies. Identification of antiepileptogenesis targets has been an overarching goal over the last decade, as current anticonvulsant medications appear to influence only the acute process of ictogenesis. Clearly, there is an urgent need to develop novel therapeutic interventions that are disease modifying-therapies that either completely or partially prevent the emergence of SRS. An important secondary goal is to develop new treatments that can also lessen the burden of epilepsy comorbidities (e.g., cognitive impairment, mood disorders) by preventing or reducing the deleterious changes during the epileptogenic process. This review summarizes novel antiepileptogenesis targets that were critically discussed at the XIth Workshop on the Neurobiology of Epilepsy (WONOEP XI) meeting in Grottaferrata, Italy. Further, emerging neurometabolic links among several target mechanisms and highlights of the panel discussion are presented.
几十年来，人们一直在使用癫痫发作和癫痫的体外和体内模型，以揭示自发性复发性癫痫（SRS）发生的分子和细胞机制 - 这是癫痫大脑的定义特征。然而，尽管我们对癫痫发作的发生有了很大的了解，但研究人员尚未开发出可靠的生物标志物和癫痫发生过程的替代标志物。可悲的是，产生癫痫状态的发病机制，特别是在头部创伤、炎症或长时间热性惊厥等诱发事件之后，还了解甚少。一个主要的挑战是已知癫痫综合征的固有复杂性和异质性，以及处于危险中的患者表现出的不同遗传易感性。因此，不太可能存在所有癫痫都共有的单一基本病理生理机制。过去十年中，鉴定抗癫痫发生靶点一直是一个首要目标，因为目前的抗惊厥药物似乎仅影响癫痫发生的急性过程。显然，迫切需要开发新的治疗干预措施，这些措施可以改变疾病的进程 - 即完全或部分预防 SRS 的出现。一个重要的次要目标是开发新的治疗方法，通过预防或减少癫痫发生过程中的有害变化，减轻癫痫合并症（例如认知障碍、情绪障碍）的负担。本综述总结了在意大利 Grottaferrata 举行的第十一届癫痫神经生物学研讨会（WONOEP XI）会议上重点讨论的新的抗癫痫发生靶点。此外，还介绍了几个靶点机制之间新兴的神经代谢联系以及小组讨论的要点。
