17β-Estradiol Prevents Blood-brain Barrier Disruption Induced by VEGF

Abstract

We performed this study to determine how pretreatment of the ovariectomized rats with 17β-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 µg 17β-estradiol 21-day release pellet was implanted in the 17β-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 ¹⁴C-α-amino isobutyric acid and volume of ³H-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 the Ki with the VEGF application in the 17β-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 17β-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 17β-estradiol treatment prevented BBB disruption induced by the VEGF in the ovariectomized rats.

Key words

Brain - Capillary permeability - Estrogen - Vascular endothelial growth factor

References

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