The Neuroprotective Effects Of Estrogens On Status Epileptics-induced Hippocampal Cell Damage

Objective: to examine whether estrogens may protect hippocampal cells of CAS subfield after status epilepticus in adult female rats and the relation between the effects of estrogens on seizures and the expression of the cell death regulatory genes Bcl-2 and Bax. METHODS: The kainic acid model was used to determine if estrogens protect hippocampal cells after status epilepticus in adult female rats(150g-175g). Rats were ovariectomized 2 weeks before hormone replacement.In group 1 and 2, beta-Estradiol benzoate (EB; 2 ug in 0.1 mL of oil) was injected subcutaneously 48 and 24 hours before seizure testing. We administered kainic acid (KA, lOmg/kg intraperitoneally) and behaviorally monitored the rats for 5 hours in group 1-4. Group 5 is a normal control group. After this time, all rats with seizures were injected with pentobarbital (PB, 50 mg/kg intraperitoneally) to terminate the seizures. Group 1 and 3 received two additional doses of EB, one immediately and one 24 hours after the seizures. Group 3 received only these two doses of EB after the seizures. Group 4 received oil instead of EB. Rats were killed 48 hours after seizures. Neuronal damage was evaluated in Nissl-stained sections with comparing the neuron numbers in the hippocampal CAS subfield. We also used immunohistochemistry technique to investigate the expression of the cell death regulatory genens bcl-2 and bax. In order to know whether the protection of estrogens is related to these genes. RESULTS: Estrogen treatment before kainic acid administration significantly delayed the onset of kainic acid-induced clonic seizures, whereas it did notchange the onset of status epilepticus compared with oil-treated groups. Furthermore, estrogen treatment significantly protected against kainic acid-induced seizure-related mortality. In group 4 , examination of Nissl-stained slides revealed severe neuronal damage in the vulnerable pyramidal neurons of the hippocampal CAS subfield.However, estrogen pretreatment, as well as the combination of pretreatment and posttreatment, showed less demaged in the CAS subfield. Posttreatment only had no protective effects.Estrogen treatment before kainic acid administration inhibited the expression of the Bax induced by seizures, but the expression of the Bcl-2 was not affected. CONCLUSIONS: Our results suggest that estrogens can be beneficial in protecting against status epilepticus-induced hippocampal damage.The inhibition to the expression of Bax may be involved the neuroprotective effects of estogens.