Ischemic neurons activate astrocytes to disrupt endothelial barrier via increasing VEGF expression.
Ischemic neurons activate astrocytes to disrupt endothelial barrier via increasing VEGF expression.
复制标题
缺血神经元通过增加 VEGF 表达激活星形胶质细胞破坏内皮屏障
DOI：
10.1111/jnc.12611
复制
发表时间：
2014-04
影响因子：
4.7
通讯作者：
Liu KJ
中科院分区：
文献类型：
--
作者：
Li YN;Pan R;Qin XJ;Yang WL;Qi Z;Liu W;Liu KJ
缺血性卒中发作后最初几小时内发生的血脑屏障（BBB）破坏与溶栓治疗后的出血性转化密切相关。然而，这种急性血脑屏障破坏的机制仍不清楚。在神经血管单元中，神经元不与内皮屏障直接接触，但它们对缺血性损伤高度敏感和脆弱，并且可能在脑缺血发生时作为破坏BBB的引发剂。在此，我们采用氧糖剥夺（OGD）和体外血脑屏障系统组成的脑微血管细胞和星形胶质细胞来验证这一假设。将神经元（CATH. a细胞）暴露于OGD 3小时，然后与内皮单层（弯曲3细胞）或内皮细胞加星形胶质细胞（C8-D1 A细胞）共培养。孵育OGD处理的神经元与内皮单层单独没有增加内皮通透性。然而，当存在星形胶质细胞时，内皮通透性显著增加，这伴随着occludin和claudin-5蛋白的丢失以及VEGF分泌到条件培养基中的增加。重要的是，当VEGF在星形胶质细胞中被siRNA敲低时，所有这些变化都被消除。我们的研究结果表明，缺血性神经元激活星形胶质细胞增加VEGF的生产，这反过来又诱导内皮屏障破坏。
Blood brain barrier (BBB) disruption occurring within the first few hours of ischemic stroke onset is closely associated with hemorrhagic transformation following thrombolytic therapy. However, the mechanism of this acute BBB disruption remains unclear. In the neurovascular unit, neurons do not have direct contact with the endothelial barrier, however they are highly sensitive and vulnerable to ischemic injury, and may act as the initiator for disrupting BBB when cerebral ischemia occurs. Herein we employed oxygen-glucose deprivation (OGD) and an in vitro BBB system consisting of brain microvascular cells and astrocytes to test this hypothesis. Neurons (CATH.a cells) were exposed to OGD for 3-hours before co-culturing with endothelial monolayer (bEnd 3 cells), or endothelial cells plus astrocytes (C8-D1A cells). Incubation of OGD-treated neurons with endothelial monolayer alone did not increase endothelial permeability. However, when astrocytes were present, the endothelial permeability was significantly increased, which was accompanied by loss of occludin and claudin-5 proteins as well as increased VEGF secretion into the conditioned medium. Importantly, all these changes were abolished when VEGF was knocked down in astrocytes by siRNA. Our findings suggest that ischemic neurons activate astrocytes to increase VEGF production, which in turn induces endothelial barrier disruption.
登录
查看更多内容
影响因子：
8.3
作者：
Hjort, Niels;Wu, Ona;Ostergaard, Leif
通讯作者：
Ostergaard, Leif
影响因子：
6.7
作者：
Schubert-Unkmeir A;Konrad C;Slanina H;Czapek F;Hebling S;Frosch M
通讯作者：
Frosch M
DOI：
10.1073/pnas.0808698106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Argaw, Azeb Tadesse;Gurfein, Blake T.;John, Gareth R.
通讯作者：
John, Gareth R.
影响因子：
3
作者：
Pehar, Mariana;Vargas, Marcelo R.;Barbeito, Luis
通讯作者：
Barbeito, Luis
影响因子：
6.3
作者：
Ezan, Pascal;Andre, Pascal;Cohen-Salmon, Martine
通讯作者：
Cohen-Salmon, Martine