Abstracts

Rationale: Hypoxic encephalopathy is the most common cause of neonatal seizures and can lead to development of epilepsy and cognitive disorders. We have previously established a model of hypoxia-induced neonatal seizures that exhibits increased susceptibility to later-life seizure susceptibility and seizure-induced neuronal death. Here, we hypothesize hypoxia-induced neonatal seizures may lead to the development of spontaneous epileptiform seizures and interictal spikes in later life. Methods: Postnatal day (P) 10 Long Evans rats were subjected to hypoxic conditions (15 min of graded exposure to 7-4% O2) and allowed to survive for up to 3 months following seizures. Five weeks following hypoxia-induced seizures, rats (n=8) were implanted unilaterally with twisted wire bipolar electrodes into the dorsal hippocampus; cortical electrodes were placed over the fronto-parietal cortex. The assembly was anchored with dental cement and stainless steel screws. Hippocampal and cortical recordings were performed via long flexible cables in freely moving, non-anaesthetized rats. Recordings were compared to iplanted control littermates (n=8). Results: Early-life hypoxia-induced seizures evoked electro-clinical spontaneous seizures in 7 and interictal events in 8 of the 8 rats experiencing neonatal seizures, Electrographic seizures recorded from rats from 4-10 weeks post P10 seizures: unilateral bipolar hippocampal electrodes revealed runs of high amplitude (at least twice background) polyspikes and/or sharp waves lasting at least 3 seconds in these rats. The behavioral correlates of these seizures consisted of sudden cessation of activity accompanied with facial automatisms, facial twitching, and head movements. Typically, head jerks followed by resumption of activity marked the end of seizures. The median frequency of epileptiform discharges in the animals that had experienced neonatal seizures was 9.33 seizures/hr as compared to 1.09 seizures/hr (n=8, p<0.005) in control littermates. In many rats, the seizure activity was also recorded from cortical electrodes, suggesting spread of epileptiform activity to the cortical circuits. Furthermore 86.4% of the recordings from rats experiencing neonatal hypoxia-induced seizures showed the presence of epileptiform activity in the recordings. In addition, the median frequency of interictal spikes in the animals that had experienced neonatal seizures was 3.1 spikes/hr as compared to 0.75 spikes/hr in control littermates (n=8, p<0.02).