Abstracts

RATIONALE: Kainic acid (KA)-induced status epilepticus results in neuronal loss in the hilus and CA3 hippocampal region. In female rats, estrogen administration at low doses has neuroprotective effect in the same regions. The neuroprotective effect of estrogen seems to be related to increased inhibition in the dentate gyrus, which serves as a gate for seizure propagation from entorhinal cortex into the hippocampus. In fact, estrogen increases paired pulse inhibition in the dentate gyrus. We used [14C]2-deoxyglucose autoradiography to determine the changes in glucose utilization (a marker of neuronal activation) in the dentate gyrus following seizures in oil- and estrogen-treated females.
METHODS: Rats were ovariectomized one week before hormone replacement. Oil vehicle or b-estradiol (2 [mu]g/day) were injected subcutaneously 48 and 24 hours prior to saline or kainic acid (16 mg/kg i.p.). Cerebral glucose utilization was measured with [14C]2-deoxyglucose, which was injected after 45 minutes of continuous seizures.
RESULTS: Qualitative evaluation of the autoradiograms following KA-induced status epilepticus revealed hypermetabolic activity in the granule cell layer in oil treated rats compared to rats without seizures. In contrast, no such hypermetabolism was observed in the granule cell layer in estrogen-treated rats.
CONCLUSIONS: These results suggest that estrogen treatment alters the entry of seizure activity into the dentate gyrus following KA-induced seizures. These findings indicate that the neuroprotective effects of estrogen on seizure-induced hippocampal damage may result from increased gating ability of the dentate gyrus.
[Supported by: NS 30387]