Can we improve the translational impact of experimental approaches in epilepsy?

After having worked for several years on animal models of schizophrenia, I realized how much working on animal models of epilepsy is facilitated by updating of the classification of epileptic syndromes. Basic science researchers have benefited from improvements in descriptions of these syndromes. In addition, in this disease, we are very lucky to have reliable biomarkers for seizures. The first one is the clinical expression of seizures that aids in characterizing the syndrome. But most importantly, we can use a powerful biomarker, namely electroencephalography (EEG), which helps tremendously in characterizing the human epileptic syndrome that we try to mimic in animals. However, there is a high price to pay for animal EEG recording. The animals must be equipped with recording devices. Before we had access to wireless systems, each animal was implanted with a recording device on its head and needed to be physically connected to a recording system. This was relatively easy in GAERS or control animals, but pilocarpine‐treated rats posed challenges. These rats were very aggressive, quite difficult to handle, and students were reluctant to work with the animals. The rats were housed alone for two main reasons. Special cages were needed to prevent them from scratching their heads on the typically low lids and damaging the recording systems. Second, because outbred male animals are naturally aggressive, they cannot be housed together in small cages. Most researchers considered the aggressive behavior of pilocarpine‐ or kainate‐treated rats as unavoidable since their brains had lesions, especially in the amygdala. Hence the research utilized isolated animals despite the fact that stress is known to be one of the main triggers of epileptic seizures in humans.6 Even now that most researchers use wireless recording systems, we tend to maintain the animals in isolated cages to prevent fights between males. Read more …

Commentary

In the three commentaries that follow, including one by the author himself, these different points are raised in more detail. The paper by Manouze et al highlights the multiplicity of factors that must be considered to improve the way we study epilepsy and interpret data in animal models of epilepsy. This is critical to reach our final goal, which is translation of animal studies to human patients. The translational task force of the International League Against Epilepsy (ILAE) has already worked quite hard to establish guidelines for translational research in epilepsy, which have been the topic of two supplements, one in Epilepsia in 2017 and one in Epilepsia Open in 2018. Those guidelines appear critical for conditions of animal housing to allow better interpretation of data and translation to the human patient as well as easier comparison between studies.

This editorial is followed by a commentary by Christophe Bernard who clarifies why he decided to perform this research, a commentary on the parameters to consider when studying animal models of epilepsy by Wolfgang Löscher, and another one on the consequences of environment on animal studies by Jean‐Christophe Cassel.

On the interpretation of results obtained in singly housed animals. Chirstopher Bernard. Epilepsia, 4 October 2019. doi 10.1111/epi.16347

Consequences of housing conditions and interindividual diversity in rodent models of acquired epilepsy. Wolfgang Löscher. Epilepsia, 4 October 2019. doi 10.1111/epi.16344

Environment is not trivial! Jean-Christophe Cassel. Epilepsia, 4 October 2019. doi 10.1111/epi.16346