Abstracts

RATIONALE: Symptomatic epilepsy accounts for up to 30%-40% of new cases of epilepsy. Status epilepticus (SE) is the first presentation of acquired epilepsy in up to 30% of these new cases. The rat pilocarpine model is useful to study acquired epilepsy in that it allows for the biochemical characterization of epileptogenesis from the initial traumatic episode (SE) through the development and expression of spontaneous recurrent seizures (epilepsy). It is well established that loss of Ca homeostasis is associated with epileptogenesis. One important neuronal Ca homeostatic mechanism is the sequestration of Ca into the endoplasmic reticulum via Mg/Ca ATPase. It was previously demonstrated in the rat pilocarpine model that Mg/Ca ATPase mediated Ca uptake in cortex microsomes (endoplasmic reticulum) was significantly inhibited acutely after 1 hour of status epilepticus (Parsons et al, J. Neurochem. 75, 1209-1218, 2000). This study was initiated to determine if SE causes inhibition of Mg/Ca ATPase-mediated Ca uptake in hippocampal microsomes and if this inhibition persists following epileptogenesis.
METHODS: Adult male Sprague-Dawley rats were subjected 1 hr SE. Following SE, animals were either sacrificed immediately or SE was terminated by DZ injection and the animals allowed to survive for up to 1 yr. Seizure expression in long-term survival animals was confirmed by visual observation. Animals were sacrificed and brain regions dissected and microsomes isolated by differential centrifugation. Mg/Ca ATPase-mediated Ca sequestration was measured using radioactive Ca and results compared to age matched controls.
RESULTS: Acutely following 1 hour of status epilepticus, Ca uptake in hippocampal microsomes was significantly inhibited at all time points measured (26.6%-47.8% inhibition, p[lt]0.05, n=3, t-test). The rate of Ca uptake was also significantly inhibited acutely following status epilepticus (37.3% inhibition, p[lt]0.05, n=3, t-test). One year after the initial episode of status epilepticus, inhibition of Mg/Ca ATPase-mediated Ca uptake in hippocampal microsomes was greater at all time points measured (55.5%-78.2% inhibition, p[lt]0.05, n=2, t-test). The rate of Ca uptake also became more significantly inhibited one year after status epilepticus (92.5% inhibition, p[lt]0.05, n=2, t-test).
CONCLUSIONS: The data demonstrate that one hour of status epilepticus significantly altered hippocampal microsomal Mg/Ca ATPase-mediated Ca uptake. The data also showed that this inhibition persisted and increased one year after the initial status episode. The results suggest that inhibition of hippocampal microsomal Ca uptake may underlie some of the plasticity changes associated with epileptogenesis.
Support: Epilepsy Foundation/American Epilepsy Society 2000 Research Training Fellowship, NSO7288, NS23350, NS25630