Abstracts

RATIONALE: Prolonged seizures in young children appear to increase the risk of development of epilepsy in adulthood. However, the mechanisms which leads to development of epilepsy in some but not in all children exposed to prolonged seizures is still not clear. We examined the development of epilepsy following prolonged seizures during development in an animal model to better understand the potential mechanisms.
METHODS: Sprague-Dawley rat pups at postnatal day 20 (P20) were injected ip with 3meq/kg lithium, followed 14-18 hrs later by 60mg/kg pilocarpine. Occurrence of status-epilepticus was confirmed by EEG and behavioural monitoring. After attaining adulthood ([gt]P90), the rats were monitored continuously for 24 hrs/day for 14 days for any sign of spontaneous behavioural seizures. Rats were then implanted chronically with electrodes in CA1 and motor cortex to monitor for appearance of spontaneous electrographic seizures. Video-EEG recordings were then obtained for an additional 5 days (6 hrs/day). The rats were then classified as epileptic (rats with 2 or more spontaneous seizures) and non-epileptic (rats with no spontaneous seizures). Brains were subsequently examined for cell loss and synaptic reorganization using cresyl violet and Timm staining.
RESULTS: 15 rats treated with lithium-pilocarpine at P20 were studied. 60% of animals developed spontaneous behavioural seizures. All 9 rats seen to have behavioural seizures also demonstrated electrographic seizures, while no electrographic seizures were seen in the 6 animals not demonstrating behavioural seizures (100% concordance). Behavioural seizures included wild running, starring, head nodding, facial clonus and stiffening of the tail, with some animals also exhibiting forelimb clonus, rearing and falling (stage 3-5 seizures). Timm and cresyl violet staining did not show any evidence of synaptic reorganization or hippocampal cell loss in animals from either group.
CONCLUSIONS: Development of epilepsy following prolonged early-life seizures does not appear to be dependent on morphological changes in the hippocampus. Our findings suggest that neither mossy fiber sprouting nor hippocampal cell loss is a necessary prerequisite for the occurrence of spontaneous seizures in this model. Further studies of functional and molecular alterations may better elucidate the mechanisms determining which animals will become epileptic following prolonged seizures during development.
Support: NIH NS38595 and Epilepsy Foundation of America to ABK