Medlej Yasser, Salah Houssein, Wadi Lara, Saad Sarah, Asdikian Rita, Karnib Nabil, Ghazal Dima, Bashir Bashir, Allam Jad, Obeid Makram
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Methods Mol Biol. 2019;2011:345-367. doi: 10.1007/978-1-4939-9554-7_20.
Psychiatric and cognitive disturbances are the most common comorbidities of epileptic disorders in children. The successful treatment of these comorbidities faces many challenges including their etiologically heterogonous nature. Translational neurobehavioral research in age-tailored and clinically relevant rodent seizure models offers a controlled setting to investigate emotional and cognitive behavioral disturbances, their causative factors, and potentially novel treatment interventions. In this review, we propose a conceptual framework that provides a nonsubjective approach to rodent emotional behavioral testing with a focus on the clinically relevant outcome of behavioral response adaptability. We also describe the battery of neurobehavioral tests that we tailored to seizure models with prominent amygdalo-hippocampal involvement, including testing panels for anxiety-like, exploratory, and hyperactive behaviors (the open-field and light-dark box tests), depressive-like behaviors (the forced swim test), and visuospatial navigation (Morris water maze). The review also discusses the modifications we introduced to active avoidance testing in order to simultaneously test auditory and hippocampal-dependent emotionally relevant learning and memory. When interpreting the significance and clinical relevance of the behavioral responses obtained from a given testing panel, it is important to avoid a holistic disease-based approach as a specific panel may not necessarily mirror a disease entity. The analysis of measurable behavioral responses has to be performed in the context of outcomes obtained from multiple related and complementary neurobehavioral testing panels. Behavioral testing is also complemented by mechanistic electrophysiological and molecular investigations.
精神和认知障碍是儿童癫痫疾病最常见的共病。这些共病的成功治疗面临诸多挑战，包括其病因的异质性。在适合年龄且与临床相关的啮齿动物癫痫模型中进行的转化神经行为研究提供了一个可控的环境，以研究情绪和认知行为障碍、其致病因素以及潜在的新型治疗干预措施。在本综述中，我们提出了一个概念框架，该框架提供了一种非主观的啮齿动物情绪行为测试方法，重点关注行为反应适应性这一与临床相关的结果。我们还描述了一系列针对杏仁核 - 海马体显著受累的癫痫模型量身定制的神经行为测试，包括焦虑样、探索性和多动行为（旷场试验和明暗箱试验）、抑郁样行为（强迫游泳试验）以及视觉空间导航（莫里斯水迷宫试验）的测试面板。该综述还讨论了我们对主动回避测试所做的修改，以便同时测试听觉和海马体依赖的情绪相关学习和记忆。在解释从给定测试面板获得的行为反应的意义和临床相关性时，重要的是要避免基于整体疾病的方法，因为特定面板不一定能反映疾病实体。必须在从多个相关且互补的神经行为测试面板获得的结果背景下对可测量的行为反应进行分析。行为测试还辅以机制性电生理和分子研究。
