Abstracts

Epilepsy ranks among the top three causes of neurological disability. In the pediatric population the estimated prevalence is 3-5%, with the highest incidence being in the first year of life; a critical neurodevelopmental timeframe. While many causative factors underlying neonatal epilepsy are known, there still remain a significant proportion of neonatal seizures with unknown etiologies. These seizures occur irrespective of social, cultural or geographical boundaries, which suggests a common pathogenic mechanism such as a cold or flu. Thus we postulated that the maternal response to these infections may effect underlying fetal neurodevelopment and seizure susceptibility. Timed- pregnant Sprague-Dawley rats were given intraperitoneal LPS to mimic a gram-negative bacterial infection (equal number of controls). Dams were given 50 or 100 [mu]g/kg LPS (or control saline) at 15 days gestation. Body temperature and any effect on pregnancy were monitored. Rat pups were assessed for general morphometric characteristics and video-monitored for spontaneous convulsions. At 14 days postnatal (P14) seizure susceptibility was determined using LPS (200 [mu]g/kg) followed by kainic acid (KA;1.75 mg/kg), an ED50 seizure dose in normal neonatal rats. Data was compared using standard statistical measures. Representative animals were selected for analysis of cortical cytoarchitecture using routine H[amp]E staining and for the immunohistochemical expression of the 27kDa Heat Shock Protein (HSP27) by standard protocols. Maternal infection had no adverse effects on pregnancy or on the general development of the pups. An increased seizure susceptibility was observed in neonatal pups from dams treated with 100 [mu]g/kg of LPS (75% had seizures) as compared to the 50 [mu]g/kg LPS and control groups (50% had seizures). This same trend was observed in pups (dams treated with 100 [mu]g/kg LPS) treated with KA only. Cortical cytoarchitecture did not reveal any gross abnormalities in the normal laminar patterns. Immunohistochemical analysis of HSP27 immunoreactivity (HSP27-ir) showed an altered pattern in the hippocampus, as compared to naive and kainic acid induced status epilepticus controls. In this study, we developed an animal model of increased neonatal seizure susceptibility as a result of low grade maternal infection, an effect that appears to be related to excitatory mechanisms. The maternal infection did not affect pregnancy or the overall development of the pups, and there were no observed spontaneous seizures in any of the groups. No obvious cytoarchitectural changes were observed, however differences were seen in hippocampal HSP27-ir as compared to controls. This model therefore may be useful for studying the mechanisms underlying seizure susceptibility as well as the potential long term complications of recurrent seizures. (Supported by University of Calgary and CIHR.)