Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain.
Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain.
复制标题
星形胶质细胞对于维持成年小鼠脑中的血脑屏障是必需的。
作者：
Heithoff BP;George KK;Phares AN;Zuidhoek IA;Munoz-Ballester C;Robel S
在成人大脑中，已知多种细胞类型产生调节血脑屏障特性的因子，包括星形胶质细胞。然而，最近的几项研究对成熟星形胶质细胞在血脑屏障中的作用提出了质疑。为了确定星形胶质细胞是否在维持成人血脑屏障中发挥非冗余和必要的功能，我们使用了他莫昔芬诱导的星形胶质细胞消融的小鼠模型。在成年小鼠中，他莫昔芬诱导在2小时内引起稀疏的凋亡星形胶质细胞死亡。指示BBB损伤的是，早在存在星形胶质细胞消融时就检测到指示BBB损伤的小分子尸胺和大血浆蛋白纤维蛋白原渗漏到脑实质中。血管内和接近星形胶质细胞损失的区域有较低的表达紧密连接蛋白zonula occludens-1，而内皮葡萄糖转运蛋白1的表达是不受干扰的。尸体泄漏持续数周，表明屏障修复不足。这与消融的星形胶质细胞未被替换的发现一致。邻近的星形胶质细胞反应为部分非增殖性星形胶质细胞增生，其特征在于形态学变化和STAT 3磷酸化延迟，这限制了消融后一个月染料渗漏到大脑和缺乏星形胶质细胞覆盖的血管表面区域。总之，星形胶质细胞是必要的，以维持血脑屏障的完整性在成人大脑。由其他细胞类型（如周细胞）分泌的血脑屏障调节因子不足以补偿星形胶质细胞的损失。成熟的星形胶质细胞对于维持成人脑中的内皮紧密连接是必需的。消融的星形胶质细胞不会被邻近星形胶质细胞的增殖或过程延伸所取代，从而导致长期的血脑屏障损伤。
In the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the blood-brain barrier. To determine if astrocytes contribute a non-redundant and necessary function in maintaining the adult blood-brain barrier, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hours. Indicative of BBB damage, leakage of the small molecule Cadaverine and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial non-proliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes one month after ablation. In conclusion, astrocytes are necessary to maintain blood-brain barrier integrity in the adult brain. Blood-brain barrier-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss. Mature astrocytes are necessary for maintenance of endothelial tight junctions in the adult brain. Ablated astrocytes are not replaced by proliferation or process extension of neighboring astrocytes, resulting in long-term blood-brain barrier damage.
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高血压期间，循环血管紧张素 II 通过破坏血脑屏障进入下丘脑和脑干。
DOI：
10.1161/hypertensionaha.113.01743
发表时间：
2014-03
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Biancardi VC;Son SJ;Ahmadi S;Filosa JA;Stern JE
通讯作者：
Stern JE
影响因子：
15.9
作者：
Horng, Sam;Therattil, Anthony;John, Gareth R.
通讯作者：
John, Gareth R.
影响因子：
3.3
作者：
Katsuno, Tatsuya;Umeda, Kazuaki;Tsukita, Sachiko
通讯作者：
Tsukita, Sachiko
影响因子：
6.3
作者：
Fleegal-DeMotta, Melissa A.;Doghu, Shinya;Banks, William A.
通讯作者：
Banks, William A.
手术引起的海马血管紧张素 II 升高通过 MMP/TIMP 导致老年大鼠血脑屏障破坏
影响因子：
5.3
作者：
Li Z;Mo N;Li L;Cao Y;Wang W;Liang Y;Deng H;Xing R;Yang L;Ni C;Chui D;Guo X
通讯作者：
Guo X