Abstracts

RATIONALE: ?-Estradiol exerts neuroprotection against hippocampal injury provoked by kainic acid induced status epilepticus in ovariectomized rats. Our study investigates the effect of estradiol on seizure-induced injury after the administration of lithium-pilocarpine. METHODS: Adult male or ovariectomized female rats were subjected to four doses of either oil vehicle (0.1ml subcutaneously) or estradiol benzoate (2?g/0.1ml subcutaneously), given at 48 and 24 hours prior to, as well as immediately after and 24 hours after the termination of status epilepticus. Seizures were induced by a combination of lithium chloride (3mmol/kg intraperitoneally) and pilocarpine (60 mg/kg intraperitoneally). Seizures were terminated with pentobarbital (50mg/kg intraperitoneally) three hours after the onset of first clonus. Rats were sacrificed 48 hours after the status. Neuronal damage of the hippocampal CA3 and hilar regions was evaluated by silver impregnation and Nissl staining. RESULTS: ??-estradiol showed a mild, but not statistically significant, proconvulsant effect in both male and female rats. There was a variability in the extent of damage. In females there appears to be less argyrophilic neurons in rats treated with ?-estradiol. This was not the case in male rats, in which there were more argyrophilic neurons in the estradiol treated rats than the controls. CONCLUSIONS: ?-estradiol has gender-specific effects on seizure-induced neuronal injury. Elucidation of the pathways responsible for these opposing effects is crucial for the design of therapeutic modalities, which would maximize the beneficial effects while minimizing the adverse effects of hormonal therapy. Supported by EFA grant.