Abstracts

Moderate to severe hypoxic-ischemic encephalopathy (HIE) occurs in 1- 2/1000 live births. Approximately 40% of the infants with HIE and neonatal seizures develop epilepsy by 4 years of age. The Levine rat pup model of hypoxia/ischemia (H/I) insult is a well characterized model of HIE. Recently, it has been reported that 40% of rat pups exposed to H/I insult at 7 days of age exhibit spontaneous seizures by 6 months of age (Epilepsia 2004; [underline]45[/underline](10):1210-1218). We hypothesize that a H/I insult will alter seizure threshold and, thus, predispose the rat to the development of spontaneous seizure activity., Seven day old Sprague-Dawley rat pups were anesthetized with isoflurane and subjected to right carotid artery ligation. After recovery, the pups were returned to their dams for 2 hours. Pups were then exposed to 8% oxygen/92% nitrogen for 2 hours. Temperature was maintained at 34.5-36^oC. Convulsive current curves for clonic (forebrain) and tonic (hindbrain) seizures were generated at 1 and 2 months after H/I insult and compared to those obtained from age- and sex-matched naive control rats ([gt] 25 rats per treatment group). Data were compared using Probit analysis (Minitab statistical software program)., Data for each seizure type is presented as CC50, the current at which 50% of the rats exhibited seizures [underline]+[/underline] standard error. A decrease in CC50 suggests increased seizure susceptibility. In naive male rats, CC50 significantly increased over time. Female naive rats had significantly deceased CC50 at 2 months of age (clonic 18.2[underline]+[/underline]0.4mA, tonic 29.2[underline]+[/underline]0.9mA) when compared to male naive rats (clonic 27.3[underline]+[/underline]0.9mA, tonic 52.6[underline]+[/underline]1.4mA). When compared to naive female rats, the CC50 for clonic seizures in female rats was significantly decreased (p=0.005) at 1 month post H/I insult but increased at 2 months (p=0.001). CC50 for tonic seizures in female naive and H/I rats did not differ. Male rats exhibited increased CC50 for tonic seizures (p=0.007) at 1 month (35.5[underline]+[/underline]1.2mA) and 2 months (61.6[underline]+[/underline]1.7mA) when compared to naive male rats (28.3[underline]+[/underline]1.7mA and 52.6[underline]+[/underline]1.4mA, respectively)., Alteration in seizure susceptibility is dependent on sex and time after H/I insult. Female rat pups exhibited enhanced clonic (forebrain) seizure susceptibility at 1 month after H/I insult but deceased susceptibility 2 months after insult. Interestingly, H/I insult in male rats decreased tonic seizure susceptibilty at 1 and 2 months after insult. Thus, H/I insult does not appear to consistently increase seizure susceptibility as evaluted by the MES method. Based on these results, it would appear that electrical population seizure threshold testing is not predictive of long-term outcome (e.g. spontaneous seizure activity)., (Supported by Primary Children[apos]s Medical Center Foundation Innovative Research Grant.)