Abstract
Objective: We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability.
Materials and Methods: Female ovariectomized Sprague-Dawley rats were replaced with estradiol (E2) and estriol (E3) (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.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the support of the American Heart Association Established Investigator Award (0540081N) and the NIH National Institutes of Neurologic Disorders and Stroke grants (NS045940, RO1 NS40071, and RO1 NSO43316). The authors also would like to thank the Totman Medical Research Trust for their continued support.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on iFirst on 9 August 2009.