17β-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats
17β-estradiol differentially regulates blood-brain barrier permeability in young and aging female rats
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DOI：
10.1210/en.2004-0984
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发表时间：
2004-12-01
期刊：
影响因子：
4.8
通讯作者：
Sohrabji, F
中科院分区：
文献类型：
--
作者：
Bake, S;Sohrabji, F
由于大脑及其血管系统都是雌激素的有效靶点，与年龄相关的雌激素水平下降或雌激素受体改变可能会破坏血脑屏障的完整性，导致有毒产物的流入增加。本研究验证了这一假设，即血脑屏障在生殖衰老动物中更具渗透性，并且与年轻成年女性相比，对雌激素替代的反应不同。将年轻成年和生殖衰老大鼠切除卵巢，并用雌激素或对照丸代替。我们发现，与年轻成年人相比，生殖衰老女性的嗅球和海马中的染料外渗增加了2至4倍。此外，雌激素显着减少染料外渗在嗅球和海马在年轻的成年人相比，年龄匹配的对照丸。然而，雌激素替代增加染料外渗在生殖衰老的女性海马与年龄匹配的控制颗粒取代动物相比，而染料外渗不变的雌激素在嗅球的衰老女性。有没有年龄和雌激素相关的差异，染料积累在脑垂体，这是一个脑室周围的器官。这些结果支持了这样的假设，即标志着生殖衰老的激素下降导致血脑屏障通透性增加，在特定区域雌激素治疗进一步加剧。
Because both brain and its vasculature are potent targets of estrogen, age-related decline in estrogen levels or alterations in estrogen receptors may disrupt the integrity of the blood-brain barrier, leading to increased influx of toxic products. The present study tested the hypothesis that the blood-brain barrier is more permeable in reproductive senescent animals and will respond differently to estrogen replacement as compared with young adult females. Young adult and reproductive senescent rats were ovariectomized and replaced with an estrogen or control pellet. We found a 2- to 4-fold increase in extravasation of dye in the olfactory bulb and hippocampus of reproductive senescent females compared with young adults. Furthermore, estrogen significantly reduced dye extravasation in both olfactory bulb and hippocampus in young adults compared with age-matched counterparts that received a control pellet. However, estrogen replacement increased dye extravasation in the hippocampus of reproductive senescent females compared with age-matched control-pellet replaced animals, whereas dye extravasation was unchanged by estrogen in the olfactory bulb of senescent females. There were no age- and estrogen-related differences in dye accumulation in the pituitary gland, which is a circumventricular organ. These results support the hypothesis that the hormonal decline that marks reproductive senescence leads to increased permeability of the blood-brain barrier, which is further exacerbated by estrogen treatment in specific regions.