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 (E۲) 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 ۱۸۲۷۸۰) were administered. Materials and Methods: Ovariectomized rats were divided into ۱۰ groups, as follows: Sham, TBI, E۲, oil, MPP+E۲, PHTPP+E۲, MPP+PHTPP+E۲, ICI+E۲, MPP, and DMSO. E۲ (۳۳.۳ µg/Kg) or oil were administered ۳۰ min after TBI. ۱ dose (۱۵۰ µg/Kg) of each of MPP, PHTPP, and (۴ mg/kg) ICI۱۸۲۷۸۰ was injected two times, ۲۴ hr apart, before TBI and estrogen treatment. BBB disruption (Evans blue content) and brain edema (brain water content) evaluated ۵ hr and ۲۴ hr after the TBI were evaluated, respectively. Results: The results showed that E۲ reduced brain edema after TBI compared to vehicle (P<۰.۰۱). The brain edema in the MPP+E۲ and PHTPP+E۲ groups decreased compared to the vehicle (P<۰.۰۰۱). There was no significant difference in MPP+PHTPP+E۲ and ICI+E۲ compared to TBI. This parameter in MPP was similar to vehicle. Evans blue content in E۲ group was lower than vehicle (P<۰.۰۵).The inhibitory effect of E۲ on Evans blue was not reduced by MPP+E۲ and PHTPP+E۲ 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 E۲-induced decrease in brain edema and BBB disruption; this may suggest that these effects were mediated via both receptors.

کلیدواژه ها:

Blood-brain-barrier ، Brain edema ، ERα antagonist ، ERβ antagonist ، ICI۱۸۲۷۸۰ ، Traumatic brain injury