Progress and Outlooks in a Genetic Absence Epilepsy Model (WAG/Rij)
G. van Luijtelaar and M. Zobeiri
Affiliation: Donders Centre for Cognition, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
The WAG/Rij model is a well characterized and validated genetic animal epilepsy model in which the for absence
epilepsy highly characteristic spike-wave discharges (SWDs) develop spontaneously. In this review we discuss first
some older and many new studies, with an emphasis on pharmacological and neurochemical studies towards the role of
GABA and glutamate and the ion channels involved in the pathological firing patterns. Next, new insights and highlights
from the last 5-10 years of reaearch in WAG/Rij rats are discussed. First, early environmental factors modulate SWD
characteristics and antiepileptogenesis is possible. Also new is that the classically assumed association between sleep
spindles and SWDs seems no longer valid as an explanatory role for the occurrence of SWDs in the genetic rodent models.
A role of cortical and thalamic glial cells has been revealed, indicating a putative role for inflammatory cytokines.
Neurophysiologic and signal analytical studies in this and in another rodent model (GAERS) point towards a cortical site
of origin, that SWDs do not have a sudden onset, and propose a more important role for the posterior thalamus than was
previously assumed. Finally it is proposed that the reticular nucleus of the thalamus might be heterogeneous with respect
to its role in propagation and maintenance of SWDs. The presence of a well-established cortical region in which SWDs
are elicited allows for research towards new non-invasive treatment options, such as transcranial direct current stimulation
(tDCS) and transcranial magnetic stimulation (TMS). The first results show the feasibility of this new approach.
Keywords: Absence epilepsy, genetic animal models, spike-wave discharges, focal type of epilepsy, network analyses, cortical
focus theory, transcranial direct current stimulation, posterior nucleus of the thalamus, reticular thalamic nucleus.
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