Abstracts

Rationale: The present study tests the hypothesis that postnatal stress can alter hippocampal networks, which in turn increases susceptibility to prolonged atypical febrile seizures (FSs) in rat pups. Our first goal is to develop a dual pathology animal model to understand the basis of FSs for their potential prevention as they are closely linked to the development of temporal lobe epilepsy.Methods: Induction of an early postnatal stress (Days 1 to 9 after birth) consisted of daily injections of corticosterone followed by hyperthermia-induced febrile seizures at P10. P10 pups were then placed at the bottom of a plexiglass box (30 30 cm), through which warm dry air (45 48oC) was circulated. Each pup remained in the box until a generalized convulsion (GC) occurred. Tonic-clonic convulsion behaviours, body temperature monitoring (using thermographic camera and Matlab analysis) and stereotaxic electrographic febrile seizure patterns (using Video-sEEG and Matlab analysis) of male and female pups were compared to vehicle injected siblings during and after the hyperthermia session at P10. Also, in order to study the possible development of hyperexcitability in the hippocampal network later in life, excitatory post-synaptic potentials (EPSPs) evoked in CA1 pyramidal cells in ACSF were studied using patch-clamp recordings on acute brain sections of P20 male rats in vitro.Results: Our data show that postnatal stress significantly lowers the latency before general seizures occurs following hyperthermia at P10 as compared to non-stressed control offspring of both sexes (FS n=30 vs FC n=28, p < 0.001 and MS n=28 vs MC n=32, p < 0.001). Using thermographic camera during this session, we found that the threshold body temperature tends to be lower in insulted pups (n=5, p < 0.05 in males only). Finally by performing EEG recordings, we found that interictal activity following hyperthermia is much more irregular and febrile seizures tend to last longer in the stressed group as compared to controls (in progress). Interestingly, ten days later,EPSP amplitudes were significantly greater at all stimulation intensities in males that underwent Stress+Hyperthermia (n=10) in comparison to the sham (n=7; p<0.001). This suggests that febrile seizure susceptibility or severity in rodents may arise in part from multifaceted hyperactivity to noxious environmental stimuli.Conclusions: HSs in rats exposed to early-life stress results in lower latency for GC, decreases the temperature threshold response and exacerbates hyperexcitability of networks as observed in EEG recording sessions at P10. Overall, these effects also points out a putatively more fragile phenotype in male as compared to female pups. Also, our preliminary data clearly indicate the presence of hyperexcitability within the double-hit CA1 network. Thus, all these results are in favour of the two-hit hypothesis of epileptogenesis and suggest a pathophysiological link between early-life stress and atypical febrile seizures, conditions that have a high prevalence in children with temporal lobe epilepsy.