Morris Gareth, Rowell Rachel, Cunningham Mark
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, Dublin, Ireland.
ALTEX. 2021;38(3):451-462. doi: 10.14573/altex.2007082. Epub 2021 Mar 10.
Advancement of understanding the etiology and treatment of epilepsy has largely depended on the use of acute and chronic animal models. An alternative approach, which is being increasingly used by a select number of laboratories worldwide, is to perform functional mechanistic studies in brain slices of living human tissue resected during surgery for drug resistant epilepsies. Pharmacoresistant epilepsy is a major clinical problem with a significant proportion of patients not receiving any symptomatic benefit from available anti-epileptic drugs. Animal models of epilepsy have dominated the landscape with regard to research and development, however they have failed to deliver new agents that would provide seizure control in patients with drug refractory epilepsy. Moreover, these models have considerable issues with respect to validity and animal welfare considerations. A compelling alternative is the use of live human epileptic tissue, which recapitulates a number of key features of refractory epilepsy. The use of live epileptic human tissue offers unprecedented opportunities to understand the mechanisms associated with difficult to treat epilepsy whilst also permitting studies of efficacy of novel agents that are being developed to alleviate epilepsy in drug resistant patients.
对癫痫病因和治疗的认识进展在很大程度上依赖于急性和慢性动物模型的使用。另一种方法正被全球一些选定的实验室越来越多地采用，即在手术切除的耐药性癫痫患者的活体脑组织切片中进行功能机制研究。药物抵抗性癫痫是一个主要的临床问题，相当一部分患者未从现有的抗癫痫药物中获得任何症状改善。癫痫动物模型在研发方面占据主导地位，然而它们未能提供能控制药物难治性癫痫患者癫痫发作的新药物。此外，这些模型在有效性和动物福利方面存在相当大的问题。一个引人注目的替代方法是使用人类癫痫活体组织，它概括了难治性癫痫的一些关键特征。使用人类癫痫活体组织为了解与难治性癫痫相关的机制提供了前所未有的机会，同时也允许对正在开发的用于缓解耐药患者癫痫的新型药物的疗效进行研究。
