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. Materials and 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. Microcirculation (2009) 16, 685-693. doi:10.3109/10739680903164131