Estrogen modulation of NMDA-induced seizures in ovariectomized and non-ovariectomized rats

The objective of this study was to examine the neuroprotective effects of estrogen in response to N-methyl-D-aspartate (NMDA)-induced seizures in both male and female rats. Thirty-eight Long-Evans rats were divided into five groups: ovariectomized females, non-ovariectomized females, ovariectomized females with estrogen replacement (10 microg 17beta-estradiol in 100 microl sesame oil), males given exogenous estrogen and males receiving no estrogen. Using stereotaxic surgery, a cannula was placed in the lateral ventricle for convulsant agent administration (20 microg of NMDA), while an electrode was placed into the hippocampus for seizure recording. Seizure activity was monitored for 20 min. Onset to first seizure, first seizure duration, seizure frequency and total duration of seizures were determined. Rats were pretreated with either sesame oil (vehicle) or estrogen given subcutaneously for 4 days prior to seizure induction on the fourth day. Rats were euthanized 72 h later and the brains removed for histological processing. Electrode and cannula placement were verified microscopically and neuronal integrity was assessed via hematoxylin and eosin staining. Total seizure number was significantly higher in the ovariectomized females compared to the non-ovariectomized females and the ovariectomized females receiving estrogen (P<0.05). Moreover, hippocampal neuronal damage following seizure induction was significant in the ovariectomized rats compared to the non-ovariectomized rats (P<0.05). Pretreatment with estrogen did not affect any of the seizure parameters measured in the male rats. We conclude that estrogen appears to be neuroprotective against NMDA-induced seizures in female ovariectomized rats.