Morphometric changes and molecular mechanisms in rat models of idiopathic generalized epilepsy with absence seizures

The idiopathic generalized epilepsies (IGEs), constituting approximately a quarter of all epilepsy cases, are presumed to arise primarily from genetic abnormalities. A minority of cases have been identified to be caused by mutations in a single gene, but in the vast majority, mutations in multiple genes are presumed to contribute to the development of epilepsy. Two rat models of IGE with absence seizures, the Genetic Epilepsy Rats from Strasbourg (GAERS) and Wistar Albino Glaxo from Rijswijk (WAG/Rij), have proven valuable for translational research. These models closely mimic the behavioural, electrophysiological, and pharmacological aspects of the human condition, with the epilepsy phenotype for both likely to have polygenic determinants. Research in these models, using molecular and in vivo imaging approaches, has provided important insights into the pathophysiology of IGE. Molecular and imaging techniques have the potential to provide researchers with tangible biomarkers of disease progression and the effects of intervention, and also to provide fundamental information about the causation and epileptogenic processes associated with IGE. This review discusses the published literature concerning the molecular changes and morphometric abnormalities identified in these models, as well as their potential relevance for human IGE.

► GAERS and WAG/Rij are rat strains which exhibit genetically-determined epilepsy.
► Molecular changes in these models can aid understanding of pathophysiology.
► Structural brain alterations (MRI) may provide disease biomarkers to track progression.