Löscher Wolfgang, Stafstrom Carl E
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
Center for Systems Neuroscience, Hannover, Germany.
Epilepsia. 2023 Jan;64(1):54-91. doi: 10.1111/epi.17433. Epub 2022 Nov 5.
It is well established that epilepsy is associated with numerous neurobehavioral comorbidities, with a bidirectional relationship; people with epilepsy have an increased incidence of depression, anxiety, learning and memory difficulties, and numerous other psychosocial challenges, and the occurrence of epilepsy is higher in individuals with those comorbidities. Although the cause-and-effect relationship is uncertain, a fuller understanding of the mechanisms of comorbidities within the epilepsies could lead to improved therapeutics. Here, we review recent data on epilepsy and its neurobehavioral comorbidities, discussing mainly rodent models, which have been studied most extensively, and emphasize that clinically relevant information can be gained from preclinical models. Furthermore, we explore the numerous potential factors that may confound the interpretation of emerging data from animal models, such as the specific seizure induction method (e.g., chemical, electrical, traumatic, genetic), the role of species and strain, environmental factors (e.g., laboratory environment, handling, epigenetics), and the behavioral assays that are chosen to evaluate the various aspects of neural behavior and cognition. Overall, the interplay between epilepsy and its neurobehavioral comorbidities is undoubtedly multifactorial, involving brain structural changes, network-level differences, molecular signaling abnormalities, and other factors. Animal models are well poised to help dissect the shared pathophysiological mechanisms, neurological sequelae, and biomarkers of epilepsy and its comorbidities.
癫痫与多种神经行为共病存在关联，且这种关联是双向的，这一点已得到充分证实；癫痫患者患抑郁症、焦虑症、学习和记忆障碍以及许多其他心理社会挑战的发生率增加，而患有这些共病的个体患癫痫的几率更高。尽管因果关系尚不确定，但更全面地了解癫痫中共病的机制可能会带来更好的治疗方法。在此，我们综述了近期关于癫痫及其神经行为共病的数据，主要讨论研究最为广泛的啮齿动物模型，并强调可以从临床前模型中获得与临床相关的信息。此外，我们探讨了众多可能混淆对动物模型新出现数据解读的潜在因素，例如特定的癫痫诱发方法（如化学、电、创伤、遗传）、物种和品系的作用、环境因素（如实验室环境、处理、表观遗传学）以及为评估神经行为和认知的各个方面而选择的行为测定方法。总体而言，癫痫与其神经行为共病之间的相互作用无疑是多因素的，涉及脑结构变化、网络水平差异、分子信号异常及其他因素。动物模型非常适合帮助剖析癫痫及其共病的共同病理生理机制、神经后遗症和生物标志物。
