Abstracts

Rationale: Hypoxic encephalopathy is the most common cause of neonatal seizures, and can lead to the development of epilepsy and other developmental and cognitive disorders. We have previously established a rodent model of perinatal hypoxic encephalopathy that exhibits seizures at post-natal day (P) 10-12, as well as increased susceptibility to later-life seizures and neuronal injury following ‘second-hit seizures’. We hypothesize that hypoxia-induced seizures in this rodent model leads to development of spontaneous seizures later in life, analogous to the clinical paradigm observed in infants suffering from hypoxic encephalopathy during the perinatal and early-term period. Methods: P10 Long Evans rats were subjected to hypoxic conditions (15 min of graded exposure to 7-4% O2). Video/electroencephalograms (video/EEG) were obtained from these animals exposed to graded global hypoxia for 3 to 6 hours via subcutaneous wire electrodes, at either 12-96 hrs (n= 5) or at 4-5 weeks (n= 5) following hypoxia. The animals were not restrained and were provided with food and water ad libitum during the recording. The video/EEGs were subsequently analyzed by a blinded investigator for the presence of epileptiform discharges. Results: Animals exposed to global hypoxia experienced later-life seizure behaviors consisting of facial twitches, body tremors, head shaking, and wet dog shakes. Correlated epileptiform/ictal EEG discharges were observed in 4/5 of 12-96 hour group and in 4/4 of the 4-5 week group Seizures in the older group were significantly more frequent ( 6.24 ± 2.71 seizures/hr) in the test period than at the earlier age group (1.78 ± 0.56 seizures/hr) (p<0.05).Conclusions: This is the first report of spontaneous seizures occurring in later life following hypoxia-induced seizures at P10. We have previously reported that early life hypoxic seizure results in long term increased hippocampal excitability (Jensen, et al J. Neurophys., 1998; 79(1):73-81), enhanced seizure susceptibility to “second-hit seizures” (Koh et al Epilepsia, 2004; 45(6):569-75), and learning deficits (Jensen, et al Epilepsia 1992; 33(6):971-80). Here we show the presence of spontaneous seizures, suggesting that this is a neonatal seizure model in which progressive epileptogenesis may be studied. (Supported by: NS31718 and Epilepsy Therapy Development Project)