Abstracts

Rationale: Epilepsy is a relatively common neurological condition with an unknown etiology in the majority of cases. Because of this, considerable effort has been made towards gaining a better understanding of the pathophysiology underlying epileptogenesis in an effort to improve treatment. In this study we sought to determine whether maternal prenatal stress affected the offspring s seizure susceptibility through modulation of the stress response.Methods: In-house bred female Long-Evans rats were subjected to a prenatal predatory stress (PPS)(cat exposure) daily from G13-G20 while a comparative group served as controls (Na ve). Prior to, and during this time period fecal samples were collected to determine maternal glucocorticoid (GLU) levels. After parturition, pups were weighed and the maternal treatment groups were sub-divided, with one-half of the litters placed in an enriched environment (EE). At 15 (P15) all pups were challenged in a model of febrile convulsions (FC: 200 g/kg of LPS followed 2.5 hours later by 1.75 mg/kg of kainic acid) and videotaped for 3 hours for behavioral scoring. Twenty-four hours later pups were euthanized and trunk blood drawn for determination of basal corticosterone (CORT) levels.Results: Maternal GLU levels in stressed dams were initially elevated (p<0.02 to p<0.0001) but gradually returned to control levels with prolonged exposure. Gestational length varied slightly between litters but there was no specific group pattern and litter sizes were equivalent. However, both male and female pups from PPS dams had significantly lower birth weights (p<0.01 to p<0.001) that persisted to P15 (p<0.002 to p<0.0001): the latter effect being fully reversed by EE. Pups from PPS dams as well as those receiving EE had higher basal CORT levels compared to Na ve controls. However, the combination of PPS+EE resulted in CORT levels that were comparable to controls. While pup seizure susceptibility was not significantly different between groups, a within group analysis revealed significant differences (p<0.05 to p<0.0001) between litters for each group suggesting individual susceptibility patterns. There were no sex differences in overall seizure susceptibility. Conclusions: These results demonstrate a litter dependent pup seizure susceptibility following maternal prenatal stress. Differential response characteristics were also found in the maternal GLU response to stress and in the pup CORT levels before and after febrile convulsions. This study highlights the importance of examining individual litter responses within subgroups as there may be interesting insights into the factors affecting individual susceptibility to developing epilepsy.