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Abstract：
Epilepsy is a chronic brain disease and, considering the amount of people affected of all ages worldwide, one of the most common neurological disorders. Over 20 novel antiseizure medications (ASMs) have been released since 1993, yet despite substantial advancements in our understanding of the molecular mechanisms behind epileptogenesis, over one-third of patients continue to be resistant to available therapies. This is partially explained by the fact that the majority of existing medicines only address seizure suppression rather than underlying processes. Understanding the origin of this neurological illness requires conducting human neurological and genetic studies. However, the limitation of sample sizes, ethical concerns, and the requirement for appropriate controls (many patients have already had anti-epileptic medication exposure) in human clinical trials underscore the requirement for supplemental models. So far, mammalian models of epilepsy have helped to shed light on the underlying causes of the condition, but the high costs related to breeding of the animals, low throughput, and regulatory restrictions on their research limit their usefulness in drug screening. Here, we present an overview of the state of art in epilepsy modeling describing gold standard animal models used up to date and review the possible alternatives for this research field. Our focus will be mainly on ex vivo, in vitro, and in vivo larval zebrafish models contributing to the 3R in epilepsy modeling and drug screening. We provide a description of pharmacological and genetic methods currently available but also on the possibilities offered by the continued development in gene editing methodologies, especially CRISPR/Cas9-based, for high-throughput disease modeling and anti-epileptic drugs testing.
摘要：
癫痫是一种慢性脑部疾病,考虑到全世界所有年龄段受影响的人数，最常见的神经系统疾病之一。自1993年以来，已经发布了超过20种新型抗癫痫药物（ASM），尽管我们对癫痫发生背后的分子机制的理解取得了重大进展，超过三分之一的患者仍然对现有的治疗方法有抵抗力。部分原因是大多数现有药物仅针对癫痫发作抑制而不是基础过程。了解这种神经系统疾病的起源需要进行人类神经系统和遗传研究。然而,样本量的限制，伦理问题，人体临床试验中对适当对照的要求(许多患者已经接受过抗癫痫药物治疗)强调了对补充模型的要求.到目前为止,癫痫的哺乳动物模型有助于揭示这种疾病的根本原因，但是与动物繁殖相关的高成本，低吞吐量，和监管限制他们的研究限制了他们在药物筛选中的有用性。这里,我们概述了癫痫建模的最新技术，描述了最新使用的黄金标准动物模型，并回顾了该研究领域的可能替代方法。我们的重点将主要放在体外，在体外，和体内幼虫斑马鱼模型有助于癫痫建模和药物筛选中的3R。我们提供了目前可用的药理学和遗传学方法的描述，以及基因编辑方法的持续发展所提供的可能性。特别是基于CRISPR/Cas9的，用于高通量疾病建模和抗癫痫药物测试。
