estrogen provides neuroprotection against brain edema and blood brain barrier disruption through both estrogen receptors α and β following traumatic brain injury

objective(s):estrogen (e2) has neuroprotective effects on blood-brain-barrier (bbb) after traumatic brain injury (tbi). in order to investigate the roles of estrogen receptors (ers) in these effects, er-α antagonist (mpp) and, er-β antagonist (phtpp), or non-selective estrogen receptors antagonist (ici 182780) were administered. materials and methods: ovariectomized rats were divided into 10 groups, as follows: sham, tbi, e2, oil, mpp+e2, phtpp+e2, mpp+phtpp+e2, ici+e2, mpp, and dmso. e2 (33.3 µg/kg) or oil were administered 30 min after tbi. 1 dose (150 µg/kg) of each of mpp, phtpp, and (4 mg/kg) ici182780 was injected two times, 24 hr apart, before tbi and estrogen treatment. bbb disruption (evans blue content) and brain edema (brain water content) evaluated 5 hr and 24 hr after the tbi were evaluated, respectively. results: the results showed that e2 reduced brain edema after tbi compared to vehicle (p<0.01). the brain edema in the mpp+e2 and phtpp+e2 groups decreased compared to the vehicle (p<0.001). there was no significant difference in mpp+phtpp+e2 and ici+e2 compared to tbi. this parameter in mpp was similar to vehicle. evans blue content in e2 group was lower than vehicle (p<0.05).the inhibitory effect of e2 on evans blue was not reduced by mpp+e2 and phtpp+e2 groups, but decreased by treatment with mpp+phtpp or ici. mpp had no effect on evans blue content. conclusion: a combined administration of mpp and phtpp or ici inhibited the e2-induced decrease in brain edema and bbb disruption; this may suggest that these effects were mediated via both receptors.