Febrile seizures: an appropriate-aged model suitable for long-term studies

Abstract

Seizures induced by fever are the most prevalent age-specific seizures in infants and young children. Whether they result in long-term sequelae such as neuronal loss and temporal lobe epilepsy is controversial. Prospective studies of human febrile seizures have found no adverse effects on the developing brain. However, adults with temporal lobe epilepsy and associated limbic cell loss frequently have a history of prolonged febrile seizures in early life. These critical issues may be resolved using appropriate animal models. Published models of hyperthermic seizures have used 'adolescent' and older rats, have yielded a low percentage of animals with actual seizures, or have suffered from a high mortality, rendering them unsuitable for long-term studies. This article describes the establishment of a model of febrile seizures using the infant rat. Hyperthermia was induced by a regulated stream of mildly heated air, and the seizures were determined by both behavioral and electroencephalographic (EEG) criteria. Stereotyped seizures were generated in 93.6% of 10-11-day-old rats. EEG correlates of these seizures were not evident in cortical recordings, but were clearly present in depth recordings from the amygdala and hippocampus. Prolonged febrile seizures could be induced without burns, yielding a low mortality (11%) and long-term survival. In summary, in infant rat paradigm of EEG-confirmed, hyperthermia-induced seizures which is suitable for long-term studies is described. This model should be highly valuable for studying the mechanisms and sequelae of febrile seizures.

Fig. 1

EEG correlates of febrile seizures in a 10-day-old rat. Electroencephalogram was obtained as described in the text. The top tracing of each panel is cortical, and the bottom tracing was recorded from a bipolar amygdala electrode. A, recorded at core temperature of 36.3°C, shows non-rhythmic waves and a movement artefact. As the hyperthermia progressed, B shows the onset of a behavioral seizure: the arrow points to a movement artifact associated with the severe tonic flexion. Rhythmic discharges of increasing amplitude are seen in the amygdala lead, while cortical activity is minimal. In C, seconds later, core temperature has been determined. Epileptic discharges are seen in the amygdala lead, while the cortical EEG shows only discrete, non-rhythmic discharges on a ‘flattened’ background. Vertical scale is 50/μV, horizontal scale is 1 s.