Abstracts

Rationale: Interleukin (IL)-1 represents a prototypical pro-inflammatory pathway that is upregulated both in experimental models as well as in human epileptogenic tissue from TLE and epilepsies associated with malformations of cortical development. We addressed whether in rats with genetic absence epilepsy (GAERS) the age-related propensity to develop spike-and-wave discharges (SWDs) is associated with a concomitant activation of the IL-1 signaling in the brain.Methods: IL-1 expression and glia activation were studied by immunocytochemistry in the forebrain of non-epileptic control Wistar rats and GAERS at postnatal days (PN)14, PN20, and PN90.Results: In Wistar rats of all ages, no detectable IL-1 immunoreactivity was observed in any of the areas studied, and glial cells showed a resting morphology. In PN14 GAERS, when no SWDs have developed yet, IL-1 immunostaining was undetectable, and, as in controls, astrocytes were not activated. In 3 out of 9 PN20 GAERS, IL-1 was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1 was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions. The changes in IL-1 induction were accompanied by increased c-fos signaling in the somatosensory cortex and some thalamic nuclei. Further, pharmacological treatment with VX-765, which selectively blocks IL-1 biosynthesis, decreases the frequency of SWDs in adult GAERS. Conclusions: IL-1 induction seems to have a role in the mechanisms underlying the occurrence of absence seizures.