17beta-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 micro g 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 (14)C-alpha-amino isobutyric acid and volume of (3)H-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 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.
Chi
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OZ
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-1977, USA. chi@umdnj.edu
Barsoum
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Wen
Y
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Liu
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Weiss
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D003692:Delayed-Action Preparations; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D042461:Vascular Endothelial Growth Factor A; D004958:Estradiol