Department of Neurology, University of Vermont, Burlington, Vermont, USA. Marilyn.
Microcirculation. 2009 Nov;16(8):685-93. doi: 10.3109/10739680903164131.
We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability.
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.
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.).
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.
我们研究了雌激素替代对穿透性脑动脉(PA)结构和功能以及血脑屏障(BBB)通透性的影响。
雌性去卵巢 Sprague-Dawley 大鼠用雌二醇(E(2))和雌三醇(E(3))替代(OVX + E;N=13),并与未替代的去卵巢动物(OVX;N=14)和完整对照(CTL,发情前期;N=13)进行比较。比较加压 PA 的被动和主动直径、百分率和被动可扩展性。此外,还比较了 Lucifer Yellow(一种跨细胞转运标志物)在脑动脉中的 BBB 通透性。
与 CTL 相比,卵巢切除术增加了 PA 的肌源性张力,而雌激素治疗并不能改善这种情况。CTL 与 OVX 和 OVX + E 相比,75mmHg 时的百分率分别为 44+/-3%、51+/-1%和 54+/-3%(均 P<0.01 与 CTL)。各组之间的被动直径或可扩展性没有差异。与 CTL 动物相比,OVX 组的 BBB 通透性增加了 500%;然而,雌激素替代恢复了屏障特性:CTL、OVX 和 OVX + E 的 Lucifer Yellow 通量分别为(ng/mL):3.4+/-1.2、20.2+/-5.3(P<0.01 与 CTL)和 6.15+/-1.2(n.s.)。
这些结果表明,雌激素替代可能对大脑小血管疾病无益,但在引起 BBB 破坏和水肿的情况下,可能会限制其破坏和水肿。