Modebadze Tamara, Morgan Nicola H, Pérès Isabelle A A, Hadid Rebecca D, Amada Naoki, Hill Charlotte, Williams Claire, Stanford Ian M, Morris Christopher M, Jones Roland S G, Whalley Benjamin J, Woodhall Gavin L
Aston Brain Centre, Aston University, School of Life and Health Sciences, Birmingham, United Kingdom.
School of Pharmacy, Hopkins Life Sciences Building, University of Reading, Whiteknights, Reading, Berkshire, United Kingdom.
PLoS One. 2016 Feb 24;11(2):e0147265. doi: 10.1371/journal.pone.0147265. eCollection 2016.
Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model's features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles.
获得性癫痫的动物模型旨在为研究人员提供工具，以帮助他们理解该疾病的获得、发展和确立过程背后的机制。通常，在全身性或局部性损伤后，易损脑区会经历一个过程，随着时间的推移，导致自发性反复癫痫发作的出现。许多此类模型利用一段强烈的癫痫活动期或癫痫持续状态，这可能与高死亡率和/或大脑大面积的整体损伤有关。这些不良因素推动了慢性癫痫模型设计的改进，例如锂 - 匹罗卡品癫痫发生模型。在此，我们展示了一种优化的慢性癫痫模型，该模型将死亡率降低至1%，同时保留了高癫痫易感性和自发性癫痫发作发展的特征。通过使用体外海马局部场电位记录作为探针，我们表明该模型不会导致CA3区神经元网络功能的显著丧失，相反，在癫痫发生过程中会出现网络动力学的细微变化，最终导致慢性癫痫状态。该模型在无整体神经元损伤的情况下具有极低死亡率和高发病率的特征，为在一群不由癫痫耐受性定义的动物中详细探索癫痫发生过程提供了机会，同时认可并遵循3R原则（即替代、优化和减少科学实验中的动物使用）。
