Abstracts

Rationale: Uninterrupted seizures in the immature brain can lead to extensive neuronal injury and epilepsy. We investigated whether brief durations of status epilepticus (SE) can result in injury and spontaneous seizures.Methods: Two-week old Wistar rats were given Li-pilocarpine and allowed to seize for varying durations (30, 90 and 120 min or uninterrupted). SE was stopped with diazepam (10 mg/kg) and phenobarbital (25 mg/kg). Some animals were implanted with bipolar electrodes to verify onset and cessation of SE. Rats were either euthanized 24 hr later for examination of acute injury using hematoxylin/eosin or Fluoro-Jade B, or allowed to mature for several months at which time they were monitored with video/EEG for spontaneous seizures and examined for afterdischarge threshold and behavioral seizure score (using a modified Racine scale). They were then euthanized for mossy fiber sprouting using Timm stain.Results: Control animals not subjected to SE, but given AEDs did not show any discernible injury. 30 min of seizures caused some extrahippocampal injury, but not overt damage to hippocampal neurons. Video/EEG monitoring did not reveal spontaneous seizures. Uninterrupted SE, meanwhile, resulted in extensive CA1 damage, and widespread extrahippocampal injury and epilepsy in 25% of the population. The afterdischarge duration was significantly longer in both experimental groups versus nonseizure rats, and they demonstrated a mean seizure score of 3.70 +/- 0.3 (30 min SE) and 3.75 +/- 0.25 (uninterrupted SE) versus 0 in controls. Conclusions: Consistent with prior observations, uninterrupted SE results in both acute neuronal injury and chronic changes in the immature brain. While 30 min of seizures did not induce epilepsy per se, other measures of excitability suggest that even brief episodes of SE are sufficient to induce long term changes. Our data suggest there exists a threshold duration of SE that will result in subsequent epilepsy. Supported by NS046516, the DAPA Foundation and AEAC