Abstracts

Neonatal hypoxia-ischemia (HI) insults have been associated with periventricular leukomalacia (PVL). As a result, affected patients are at an increased risk for developing mental retardation, epilepsy and/or cerebral palsy. The Levine model of HI has been modified such that the degree and length of hypoxia (6% for 1 hour) leads to a specific reduction in myelin basic protein (MBP) and decreased seizure threshold to kainic acid (KA) at P11 (Levine [italic]Am J Pathol[/italic] 1960;36:1-17;Follett et al [italic]JNeurosci[/italic] 2004;24:4412-20; Koh et al [italic]Epilepsia[/italic] 2004;45:569-75). Thus, using this 6% rat model of PVL we evaluated the effect of HI on KA-induced seizure threshold and amygdala kindling aquisition. Additionally animals were monitored for the presence of spontaneous ictal discharges., Post-natal day 7 (P7) Sprague-Dawley rat pups were anesthetized with isoflurane and their right carotid artery ligated. Pups were allowed to recover for at least 1.5 hours and were then placed in a 6% O[sub]2[/sub] chamber for one hour; body temperature was maintained at 35[deg]C using a heating pad. Males and females from several litters were divided into HI-lesioned and naive controls. Two pups were sacrificed at P11 and MBP damage was confirmed by immunohistochemistry. The remaining animals (P90-120) were subjected to either 10mg/kg KA (males: HI n=8, naive n=12; females: HI n=6, naive n=10) or amygdala kindling (males: HI n=5; naive n=6; females: HI n=9; naive n=14). At 9 months of age five animals were monitored for the presence of spontaneous seizures using implanted surface electrodes., HI at P7 resulted in significant loss of MBP at P11. To assess KA susceptibility the following endpoints were measured: latency to 1^st,2^nd ,3^rd,4^th seizures, latency to wet dog shakes, total seizure number, number of stage III and V seizures, latency to stage III and V seizures, and incidence of death. Among these endpoints no difference in KA seizure threshold was evident between HI and naive rats regardless of sex. There was no significant difference in amygdala kindling aquisition (male or female). However, the after-discharge threshold of male HI rats was lower than that of naive rats (HI = 140mA +/- 53; naive = 207mA +/- 21). Three (2 males and 1 female) of the 5 rats (3 males and 2 females) exhibited spontaneous electrographic bursts., Consistent with previous reports, we observed marked damage to MBP four days post HI (P11). Furthermore, HI-injured rats displayed a reduced amygdala after-discharge threshold. Consistent with a previous report using the Levine model, HI rats displayed spontaneous electrographic bursting (Williams et al [italic]Epilepsia[/italic] 2004;45:1210-1218). Future video-EEG studies will evaluate the ontogeny of EEG bursts and assess the severity of clinical seizures., (Supported by Pediatric Pharmacology Program, Dept. of Pediatrics, University of Utah (LAF).)