Abstracts

Rationale: Our previous data have demonstrated that physiologic doses of -estradiol (E2) replacement have neuroprotective effects in the hilus of dentate gyrus after kainic acid (KA)-induced status epilepticus in ovariectomized female rats. This experiment determines the in vitro functional outcome of estrogen neuroprotection. Methods: Adult female rats were ovariectomized. After a week recovery, they received two-day replacement therapy with E2 (2 g in sesame oil s.c. per day). Then, status epilepticus was induced with KA (16 mg/kg i.p.) and after 5 hours all rats received 50 mg/kg of pentobarbital i.p., and additional 2 doses of E2 (immediately after the seizures and 24 hours later). Control rats received vehicle instead of E2. Forty eight hours after the status, the rats were decapitated under ether anesthesia, and hippocampal slices were prepared. Evoked population spikes were recorded in the granule cell layer after mixed perforant path stimulation with paired pulses (interstimulation interval 10-1000 ms). Results: A significant difference between the slices from controls and E2-treated rats was recorded at the 70-750 ms interstimulation intervals. At all these intervals, there was a significant potentiation of the second response in slices from controls compared to slices from E2-treated rats. Additional experiments using 400 M of GABA(B) receptor antagonist CGP 35348 indicate that this increase in paired pulse inhibition is not due to preservation of GABA(B) elements. CGP 35348 diminished the difference between the groups only at interstimulation intervals up to 200 ms. Conclusions: E2 neuroprotection in the dentate gyrus is associated with preserved late paired pulse suppression after KA-induced status epilepticus, which is not due to GABA(B) inhibition.