Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus

Purpose: Estrogens have neuroprotective effects in ischemia, stroke, and ot her conditions leading to neuronal cell death (e.g., Alzheimer's disease). The present study examined whether estrogens may have neuroprotective effec ts after seizures. Methods: The kainic acid model was used to determine if estrogens protect h ippocampal cells after status epilepticus in adult female rats. Rats were o variectomized I week before hormone replacement. beta-Estradiol benzoate (E B; 2 mu g in 0.1 mt of oil) was injected subcutaneously 38 and 24 hours bef ore seizure testing. We administered kainic acid (16 mg/kg intraperitoneall y) and behaviorally monitored the rats for 5 hours. After this lime, all ra ts were injected with pentobarbital (50 mg/kg intraperitoneally) irrespecti ve of seizure severity. Some rats received two additional doses of EB, one immediately and one 24 hours after the seizures. Another group of rats rece ived only these two doses of EB after the seizures, and yet another,group o f rats received pretreatment with the intracallular EB receptor antagonist tamoxifen before each of four EB injections. Control rats received oil inst ead of EB. Rats were killed 48 hour after seizures. Neuronal damage was eva luated in silver-impregnated and Nissl-stained sections. Results: Estrogen treatment before kainic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did n ot change the onset of status epilepticus compared with oil-treated control s. Furthermore, estrogen treatment significantly protected against kainic a cid-induced seizure-related mortality. In control rats, examination of Niss l-stained and silver-impregnated slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CA3 subfield and in the hilus of the dentate gyrus. Estrogen pretreatment, as well as the combinat ion of pretreatment and posttreatment, significantly reduced the number of argyrophilic neurons in both the CA3 and the dentate gyrus. Posttreatment o nly had no protective effects. The data indicate that intracellular EB rece ptors mediate this type of neuroprotective effect, because the tamoxifen pr etreatment abolished EB neuroprotection. Conclusions: Our results suggest that estrogens can be: beneficial in prote cting against status epilepticus-induced hippocampal damage. Hormonal condi tions may have differential effects on underlying epileptic state in some p atients. Therefore, more studies are necessary to determine the prospective therapeutic advantage of hormonal treatment in seizure-related damage.