17β-estradiol prevents blood-brain barrier disruption induced by VEGF

We performed this study to determine how pretreatment of the ovariectomized rats with 17beta-estradiol could affect blood-brain barrier disruption caused by the vascular endothelial growth factor (VEGF), an important mediator of vascular permeability. Ovariectomized female rats aged twelve to fourteen weeks were used in the study. A 500 mug 17beta-estradiol 21-day release pellet was implanted in the 17beta-estradiol group, and a vehicle pellet was implanted in the control group 21 days before the experiments. We performed three craniotomies under isoflurane anesthesia to expose cerebral cortices. Normal saline, 10(-10)M and 10(-9)M VEGF patches were applied on each hole for 30 min. The transfer coefficient (Ki) of C-14-alpha-amino isobutyric acid and volume of H-3-dextran (70,000 dalton) distribution were determined to measure the degree of BBB disruption. Ki was increased by 108% and 138% with 10(-10)M and 10(-9)M VEGF respectively-after VEGF application in the control group (p < 0.01). However, there was no significant increase in them Ki with the VEGF application in the 17beta-estradiol group, and their values were significantly lower than the corresponding data of the control group (10(-10)M: -55%,10(-9)M: -52%, p < 0.05). The volume of dextran distribution in the control group increased by 47% with VEGF 10(-9)M (p < 0.05), whereas there was no significant change in the volume of dextran distribution with VEGF application in the 17beta-estradiol group and the volume was lower than the corresponding volume of the vehicle-treated control group (10(-10)M: -34%, 10(-9)M: -32%, p < 0.05). In conclusion, our study demonstrated that chronic 17beta-estradiol treatment prevented BBB disruption induced by the VEGF in the ovariectomized rats.