Effect of a novel prolonged febrile seizure model on GABA associated ion channels

Prolonged febrile seizures are usually modelled in animals using hyperthermia as an inducer. In this study, a modified simple febrile seizure model using a combination of lipopolysaccharide (LPS) and kainic acid (KA) was used to develop a prolonged febrile seizure animal model, which we used to assess effects on the expression of the sodium– potassium–chloride cotransporter 1 (NKCC1) and potassium-chloride cotransporter 2 (KCC2) and their possible role in seizure exacerbation. At post-natal day (PND) 14, rat pups were divided into a saline (S), simple febrile seizure (FS A- ), prolonged febrile seizure (FS B- ), saline A (S A+ ) and saline B (S B+ ) groups. S A+ and S B+ groups received different concentrations of KA (1.75 mg/kg, 1.83 μg/kg respectively) but no LPS. Changes in temperature, seizure activity and duration were recorded. Gene and protein expression of NKCC1, KCC2 and KCC2 phosphorylated serine (KCC2 ser) 940 were measured 1 h post seizure termination and on PND 15 using RT- PCR and western blot. There was an initial increase in temperature that was immediately followed by a temperature decrease and an increase in seizure severity and duration in the FS B- group. There was a decrease in KCC2 ser 940 protein expression. NKCC1 protein expression was increased in both FS groups suggesting decreased GABA receptor functionality. Therefore, the novel FS B- model resulted in more severe and sustained seizure activity by altering cotransporter gene and protein expression. This suggests that this model can be used to mimic prolonged febrile seizures and hence can be used to investigate the physiological changes accompanying this condition.