Effects of 17β-estradiol on blood-brain barrier disruption during focal ischemia in rats

This study was performed to test whether 17beta-estradiol could attenuate the blood-brain barrier disruption caused by middle cerebral artery occlusion in the ovariectomized rats. Rats aged twelve to fourteen weeks were used in this study. Their ovaries were removed one week prior to the implantation of the pellets. For the 17beta-estradiol group, a 500 mug 17beta-estradiol 21 day-release pellet was implanted and for the control group, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion under isoflurane anesthesia, the transfer coefficient of C-14-alpha-aminoisobutyric acid (104 Daltons) and the volume of H-3-dextran (70 000 Daltons) distribution were determined to represent the degree of blood-brain barrier disruption. Blood pressures and blood gases were similar between controls and 17beta-estradiol-treated rats. In both groups, the transfer coefficient of the ischemic cortex was higher than that of the corresponding contralateral cortex (control: Ischemic Cortex 12.5 +/- 5.9 mul/g/min, Contralateral Cortex 3.0 +/- 1.6, p < 0.001; 17beta-estradiol: Ischemic Cortex 6.7 +/- 3.3 mul/g/min, Contralateral Cortex 2.2 +/- 0.9, p < 0.01). There was no significant difference in the transfer coefficient of the contralateral cortex between these two groups. However, the transfer coefficient of the Ischemic Cortex of the 17beta-estradiol-treated animals was 46% lower than that of the control, vehicle-treated rats (p < 0.05). The increase of the volume of H-3-dextran distribution with middle cerebral artery occlusion was significant in the vehicle-treated rats (Ischemic Cortex: 6.4 +/- 2.7 ml/100 g, Contralateral Cortex: 3.8 +/- 0.8, p < 0.01) but not in the 17beta-estradiol-treated animals. Our data suggest that chronic 17beta-estradiol treatment was effective in reducing blood-brain barrier disruption during focal ischemia in the ovariectomized rats.