The effect of ovariectomy and estrogen on penetrating brain arterioles and blood-brain barrier permeability.
OBJECTIVE
We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability.


METHODS
Female ovariectomized Sprague-Dawley rats were replaced with estradiol (E(2)) and estriol (E(3)) (OVX + E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone, and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries.


RESULTS
Ovariectomy increased myogenic tone in PA, compared to CTL, that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX + E was 44+/-3% vs. 51+/-1% and 54+/-3% (P<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals; however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX, and OVX + E was (ng/mL): 3.4+/-1.2, 20.2+/-5.3 (P<0.01 vs. CTL), and 6.15+/-1.2 (n.s.).


CONCLUSIONS
These results suggest that estrogen replacement may not be beneficial for small-vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it.
Cipolla
Marilyn J
MJ
Department of Neurology, University of Vermont, Burlington, Vermont, USA. Marilyn. Cipolla@uvm.edu
Godfrey
Julie A
JA
Wiegman
Marchien J
MJ
D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply*; D004487:Edema / Q000188:drug therapy; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D004958:Estradiol; D004964:Estriol