Abstracts

Epilepsy ranks among the top three causes of neurological disability. In the pediatric population, seizure prevalence is estimated at 3-5%, the highest incidence of which is in the first year of life. This is a critical neurodevelopmental epoch and the long-term consequences of these neonatal seizures are not fully known. Thus we sought to determine whether maternal infection alone, or in combination with a neonatal febrile convulsion, affected subsequent seizure susceptibility as well as memory and learning in adults., Timed-pregnant Sprague-Dawley rats were administered either lipopolysaccharide (LPS; 100 [micro]g/kg, i.p.) or saline (sal; control) on gestational day 15 (G15), to mimic a gram-negative bacterial infection. On postnatal day 14 (P14), febrile convulsions (FC) were induced with LPS (200 [micro]g/kg) and kainic acid (KA; 1.75 mg/kg), which is known to evoke seizures in about 50% of rats at this age. Two months later, all groups were subjected to learning and memory tasks both before and after an adult seizure. One week prior to evocation of an adult seizure with KA (15 mg/kg) rats were subjected to a contextual fear conditioning paradigm. One week after the adult seizure, rats were then tested for learning and memory in a water maze paradigm. Adult seizures were attenuated within 30 minutes of seizure onset with parenteral diazepam (5 mg/kg) to mimic clinical practice., Prenatal LPS exposure resulted in a trend towards increased neonatal seizure susceptibility at P14 compared to saline-treated controls. Further, a subset of animals with a history of prenatal LPS and FCs showed deficits in learned fear to contextual stimuli compared to cohorts of animals with no prenatal LPS and FC. Rats with a history of prenatal inflammation and postnatal FCs showed enhanced susceptibility to seizures as adults, compared to the control condition (no maternal treatment but suffered FCs). Results of the spatial learning water maze task revealed no statistically significant differences between any groups of rats regardless of prenatal treatment or FC outcome, when the KA provoked seizure were attenuated at 30 minutes., In this study, our findings suggest that prenatal LPS in combination with a neonatal FC alters adult seizure threshold as well as impairs memory performance to contextual fear stimuli. The lack of effect of adult seizure (in any group) on water maze testing, when seizures were attenuated, further emphasizes the importance of early seizure intervention., (Supported by Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), and the Alberta Heritage Foundation for Medical Research (AHFMR).)