Abstracts

Rationale: The pro-inflammatory cytokine interleukin(IL)-1β is rapidly synthesized in the rodent brain during seizures, and it is increased in epileptogenic tissue of drug resistant epilepsy patients. Pharmacological and genetic studies in rodent models of seizures indicate that increased brain levels of IL-1β play an important role in the mechanisms of ictogenesis. In addition, intracerebral administration of IL-1β has proconvulsant effect, whereas anti-IL-1β treatments (Caspase-1 inhibition and IL-1 receptor antagonist) provide powerful anticonvulsant effects. GAERS represent one of the best characterized model for studying absence seizures. Since these rats display spontaneous and reproducible spike and wave discharges (SWDs) with an age-dependent onset: no SWDs are observed in rats until postnatal (PN) 20-30 days, and the percentage of GAERS with SWDs increases with age, with their maximal expression at 3 months. The aim of this study was to investigate whether the age-related propensity of GAERS rats to develop SWDs is associated with a concomitant activation of the IL-1β system in the brain. Methods: The pattern of IL-1β, microglia (CD-11b) and astrocytes (GFAP) was evaluated by immunohistochemistry and double-immunostaining in male Wistar (used as controls) and GAERS rats at postnatal day (PN) 20 and in 3 month-old rats. Specific immunostaining was analyzed in frontoparietal cortex, thalamic nuclei and hippocampus.Procedures involving animals and their care were conducted in conformity with the university and national guidelines (36-2008.MAR)and international laws and polices. Results: In PN20 and adult Wistar control rats (n=5 each experimental group), no detectable IL-1β immunoreactivity was observed in any of the areas studied, and glial cells showed a resting morphology. The changes found in GAERS were restricted to the frontoparietal cortex, including the perioral region. In 50 % of PN20 GAERS (n=4), IL-1beta was expressed by scattered activated astrocytes, while in the remaining rats no IL-1beta staining was observed. In 3 month-old GAERS (n=4), IL-1beta immunostaining was observed in numerous reactive astrocytes. Microglia was not activated and did not express IL-1beta in PN20 or 3 month-old GAERS. Conclusions: These results show the age-dependent induction of IL-1β in GAERS in a brain region involved in SWD generation. Since IL-1β expression seems to be associated with the onset of SWDs, it may play a role in the underlying epileptogenic mechanisms.