Garcia-Cairasco Norberto, Umeoka Eduardo H L, Cortes de Oliveira José A
Physiology Department, Ribeirão Preto School of Medicine, University of São Paulo, Brazil; Neuroscience and Behavioral Sciences Department, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
Physiology Department, Ribeirão Preto School of Medicine, University of São Paulo, Brazil; Neuroscience and Behavioral Sciences Department, Ribeirão Preto School of Medicine, University of São Paulo, Brazil.
Epilepsy Behav. 2017 Jun;71(Pt B):250-273. doi: 10.1016/j.yebeh.2017.04.001. Epub 2017 May 11.
In the context of modeling epilepsy and neuropsychiatric comorbidities, we review the Wistar Audiogenic Rat (WAR), first introduced to the neuroscience international community more than 25years ago. The WAR strain is a genetically selected reflex model susceptible to audiogenic seizures (AS), acutely mimicking brainstem-dependent tonic-clonic seizures and chronically (by audiogenic kindling), temporal lobe epilepsy (TLE). Seminal neuroethological, electrophysiological, cellular, and molecular protocols support the WAR strain as a suitable and reliable animal model to study the complexity and emergent functions typical of epileptogenic networks. Furthermore, since epilepsy comorbidities have emerged as a hot topic in epilepsy research, we discuss the use of WARs in fields such as neuropsychiatry, memory and learning, neuroplasticity, neuroendocrinology, and cardio-respiratory autonomic regulation. Last, but not least, we propose that this strain be used in "omics" studies, as well as with the most advanced molecular and computational modeling techniques. Collectively, pioneering and recent findings reinforce the complexity associated with WAR alterations, consequent to the combination of their genetically-dependent background and seizure profile. To add to previous studies, we are currently developing more powerful behavioral, EEG, and molecular methods, combined with computational neuroscience/network modeling tools, to further increase the WAR strain's contributions to contemporary neuroscience in addition to increasing knowledge in a wide array of neuropsychiatric and other comorbidities, given shared neural networks. During the many years that the WAR strain has been studied, a constantly expanding network of multidisciplinary collaborators has generated a growing research and knowledge network. Our current and major wish is to make the WARs available internationally to share our knowledge and to facilitate the planning and execution of multi-institutional projects, eagerly needed to contribute to paradigm shifts in epileptology. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
在癫痫和神经精神共病建模的背景下，我们回顾了25多年前首次引入国际神经科学界的威斯塔听源性大鼠（WAR）。WAR品系是一种经基因选择的反射模型，易发生听源性癫痫发作（AS），能急性模拟脑干依赖性强直阵挛性发作，并能慢性（通过听源性点燃）模拟颞叶癫痫（TLE）。开创性的神经行为学、电生理学、细胞和分子实验方案支持WAR品系作为一种合适且可靠的动物模型，用于研究癫痫发生网络典型的复杂性和涌现功能。此外，由于癫痫共病已成为癫痫研究中的一个热门话题，我们讨论了WAR在神经精神病学、记忆与学习、神经可塑性、神经内分泌学以及心肺自主调节等领域的应用。最后但同样重要的是，我们建议将该品系用于“组学”研究以及最先进的分子和计算建模技术。总的来说，开创性和近期的研究结果强化了与WAR改变相关的复杂性，这是其基因依赖性背景和癫痫发作特征相结合的结果。为了补充先前的研究，我们目前正在开发更强大的行为、脑电图和分子方法，并结合计算神经科学/网络建模工具，以进一步增加WAR品系对当代神经科学的贡献，同时增加对广泛的神经精神和其他共病的认识，因为存在共享神经网络。在对WAR品系进行研究的多年里，一个不断扩大的多学科合作网络产生了一个不断增长的研究和知识网络。我们目前的主要愿望是在国际上提供WAR，以分享我们的知识，并促进多机构项目的规划和实施，这对于推动癫痫学范式转变非常必要。本文是名为“遗传和反射性癫痫、听源性癫痫发作及品系：从实验模型到临床”的特刊的一部分。
