Abstracts

Rationale: Recent evidence from experimental animals and humans has revealed a putative role for the pro-inflammatory cytokine IL-1β in seizures and their sequelae. Of interest is the role that this cytokine plays in developmental seizures. While the role of IL-1β in special cases such as febrile seizures appears clear, we were interested in determining if IL-1β played a role in the phenomena of developmental kindling. Methods: Male rat pups from timed pregnant Sprague-Dawley rats were used in these experiments. On postnatal day 13 (P13, date of birth = P0) separate litters of animals were prepared for amygdala kindling. Combination cannula/bipolar electrodes were aimed at the left basolateral amygdala using stereotaxic techniques. Upon completion of surgery animals were placed back with their dams and allowed to recover until P15. Before assessing the AD threshold, animals were assigned to either a vehicle or IL-1β group. IL-1β was given in a dose of 20ng/rat delivered in a solution of 1μl/rat directly into the basolateral amygdala , vehicle (PBS) was given in the same volume to control rats. In order to determine the AD threshold, we began stimulation at 25μA and increased in increments of 25μA (2 min separation between stimulations) until an AD of at least 4 sec was produced in each animal. After the initial AD threshold was determined all animals were stimulated at 400μA and kindling rate was assessed as the number of stimulations required to elicit 5 consecutive stage 4 or higher seizures. Results: IL-1β treatment resulted in a trend towards a reduction in the AD threshold. In addition to this trend IL-1β caused a significant facilitation of the early stages of kindling (# stimulations to stage 1 and 3 seizures, t-test, p < 0.05, IL-1β vs vehicle). Despite this early facilitation IL-1β did not affect the overall kindling rate to achieve 5 consecutive stage 4 seizures. In addition there were no differences found in the duration of EEG recorded seizures at any of the seizure stages. Conclusions: We have shown here that the pro-inflammatory cytokine IL-1β partially affects kindling in developing animals. While IL-1β only showed a trend towards a decrease in seizure threshold, it did facilitate early kindled seizures. This finding is in line with recent data that has shown a facilitatory role of this cytokine in models of febrile seizures during a similar developmental time period. Supported by: Natinoal Institutes of Health NS20253, NS058303 and the Heffer Family Foundation