Abstracts

Rationale: Febrile seizures (FS) are the most common type of seizures in humans, affecting up to 5% of children before the age of 5, and temporal lobe epilepsy (TLE) is the most frequent form of medication-refractory epilepsy in patients referred for epilepsy surgery. Current evidence suggests a plausible link between prolonged febrile seizures and an increased risk of developing TLE, although the magnitude of the risk is not accurately known. In retrospective studies of patients with TLE due to hippocampal sclerosis, 30-80% have a history of prolonged febrile seizures [1]. We aim to examine the correlation between these two conditions using Zebrafish, a recently established model of FS. Methods: Zebrafish 5 days post fertilization were placed in embryo medium in an incubator bath and exposed to hyperthermic temperatures. A FS was defined as reaching a minimum of stage 2 on the Zebrafish seizure scale [2]. Zebrafish that underwent a FS were reared to 1 month of age and then exposed to pentylenetetrazol (PTZ) 0.5mM for 30min. Percentage of PTZ-induced seizures, average number, latency, and duration of seizures were examined for the following groups (n =50/group): control (no FS), FS for 30min (FS30), and FS for 60min (FS60). Results: FS Zebrafish had a significantly increased sensitivity to 0.5mM PTZ (p<0.05). PTZ-induced seizures occurred in 7% of Control Zebrafish compared to 58% of FS30 and 65% of FS60 animals. A significant difference (p<0.05) was also found between FS and control groups in the average duration of induced seizures with seizure duration in control, FS30, and FS60 animals being for 8.0±2.7s, 101.2±26.4s, and 83.1±19.1s respectively. FS30 fish had a significantly greater average number of convulsions than control fish (12.9±2.7 and 2.0±0.4, respectively, p<0.05). No difference in latency to first seizure was seen between groups. Conclusions: This study establishes Zebrafish as a model for investigating the epileptogenic effects of FS. We have demonstrated that hyperthermic seizures early in development lead to a reduced seizure threshold at one month. However, there does not appear to be a difference between Zebrafish that underwent a 30 min FS versus a 60 min FS. Future studies will investigate additional FS durations as an experimental analog of simple versus complex seizures in humans and establish molecular and network changes associated with FS. [1]Cendes, F & Andermann, F 2002. Do febrile seizures: promote temporal lobe epilepsy? Retrospective Studies. In: Baram, T. Z. & Shinnar, S. (eds.) Febrile Seizures. San Diego, CA: Academic Press p77-85. [2]Baraban S et al. Pentylenetetrazole-Induced Changes in Zebrafish Behavior, Neural Activity, and c-fos Expression. Neuroscience 2005; 131:759-768.