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.