Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.
The WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial 'insult' responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then non-genetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.
Science of Health Department, School of Medicine, University of Catanzaro, Italy. Electronic address: erusso@unicz.it.
Emilio
E
Russo
Science of Health Department, School of Medicine, University of Catanzaro, Italy.
Rita
R
Citraro
Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London, United Kingdom.
Andrew
A
Constanti
Science of Health Department, School of Medicine, University of Catanzaro, Italy.
Antonio
A
Leo
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Institute of Physiology I, Westfälische Wilhelms University, Münster, Germany.
Annika
A
Lüttjohann
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Gilles
G
van Luijtelaar
Science of Health Department, School of Medicine, University of Catanzaro, Italy.
Giovambattista
G
De Sarro
D000818:Animals; D001921:Brain; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence; D051379:Mice; D051381:Rats; D012640:Seizures
Antiepileptic drugs; Epileptogenesis; Genetic animal model; Spontaneous chronic absence seizures; WAG/Rij rats