Lipopolysaccharide-induced Febrile Convulsions in the rat: Short-term sequelae

Abstract

Purpose: Febrile convulsions (FCs) occur in children as a result of fever. The mechanisms involved in the genesis of FCs and their long-term consequences on brain development remain unclear. We have developed a model of FC, by using fever as a parameter, to test the hypothesis that fever can lower seizure threshold and to examine the neurologic sequelae of FCs. Methods: Fourteen-day-old rat pups equipped with body-temperature telemetry devices exhibited ∼1.5°C fevers after lipopolysaccharide (Escherichia coli, 200 μg/kg). During such fevers, concurrently administered doses of kainic acid that are normally subconvulsant were used to induce convulsions with fever. Animals were then killed at varying times for pathological and immunohistochemical studies. Results: The pairing of lipopolysaccharide and subconvulsant kainic acid resulted in convulsions in ∼50% of febrile animals. with very low mortality. To study the neural correlates of these FCs, we used fos immunohistochemistry and found that animals with FCs had fos-positive immunoreactivity in brain regions involved in seizures. After a period of 72 h, we also examined brains for pathologic changes and found no differences among our groups. Conclusions: Our data indicate that a neuroimmune challenge and its accompanying fever reduce the seizure threshold. Furthermore, the FCs induced by fever in this model do not have short-term adverse effects on the brain. In addition, this model, by incorporating physiologic fever, may be useful for examining the role of fever and its constituent mediators in the genesis of FCs.