Aquaporin 4 Expression and Protective Role of Sex Steroids on Trauma-Induced Brain Injury in Female Rats

The brain damage caused by trauma is the most common cause of death. The neuroprotection effects of estrogen and progesterone have been reported in numerous studies. In the present study, the role of different doses of sex steroids has been investigated on the aquaporin 4 protein concentration changes in brain tissue of ovariectomized (OVX) rats after traumatic brain injury (TBI). In this experimental interventional study, 140 female rats N-MRI were randomly divided into seven groups and each group group further subdivided into two subgroups as follows; sham group, ovariectomized sham group, vehicle, physiologic and pharmacologic estrogen at doses 33.3 µg/kg, and 1 mg/kg respectively, physiologic and pharmacologic progesterone at doses 1.7 mg/kg and 8 mg/kg group. TBI was induced for groups 3-7 by Marmarou method. Thirty minutes after TBI, the hormones were intraperitoneally injected. Parameters such as Evans blue content, and water content and aquaporin 4 concentration were determined 5h and 24h after TBI respectively. Compared to the vehicle group, physiologic and pharmacologic doses of estrogen could significantly diminish the aquaporin 4 expression and water content (p<0.01), and permeability of blood - brain barrier (p<0.001). While physiologic and pharmacologic doses of progesterone had a same effect as estrogen on brain water content (p<0.001), this effect was not observed on aquaporin 4 expression. The brain Evans blue content at physiologic dose of progesterone was significantly lower than vehicle group, but it was higher at pharmacologic dose (p<0.001). We concluded that only physiologic and pharmacologic doses of estrogen reduce d the aquaporin 4 expression in OVX rats after TBI. Based on our results, estrogen may have a therapeutic effect on brain injury.