Febrile convulsions induced by the combination of lipopolysaccharide and low-dose kainic acid enhance seizure susceptibility, not epileptogenesis, in rats

Purpose: Febrile convulsions (FCs) are seizures that occur as a result of fever. Retrospective clinical studies show a large percentage of adults with temporal lobe epilepsy have a positive history of FCs, but it is unknown whether FCs during infancy alter susceptibility to developing late epilepsy. We have tested the hypothesis that FCs affect seizure susceptibility and epileptogenesis in adults. Methods: A novel model of FCs was used, in which lipopolysaccharide (LPS, Escherichia coli), in combination with a subconvulsant dose of kainic acid, caused FCs in 50% of 14-day-old male rats. Eight to 10 weeks later, electrodes were implanted into the basolateral amygdalae of all rats. After completion of the kindling procedure, animals were killed and brains examined for neurodegeneration by using Fluoro-Jade histochemistry. Results: Amygdala stimulation revealed that rats that had a FC as pups had lower afterdischarge thresholds and longer afterdischarge durations when compared with rats that received the same treatment but did not convulse. Despite this, when kindled daily, rats that had FCs as pups kindled at the same rate as did controls. However, an increase in the number of degenerating neurons was noted within the hippocampus of rats with a previous FC. Conclusions: These results suggest that, although FCs during infancy can reduce seizure thresholds, it does not facilitate epileptogenesis in adulthood. Our results indicate that FCs affected local circuits in the amygdala and possibly in the hippocampus but not circuits responsible for seizure generalization.