Maintaining Blood-Brain Barrier Integrity: Pericytes Perform Better Than Astrocytes During Prolonged Oxygen Deprivation
Maintaining Blood-Brain Barrier Integrity: Pericytes Perform Better Than Astrocytes During Prolonged Oxygen Deprivation
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DOI：
10.1002/jcp.21638
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发表时间：
2009-03-01
影响因子：
5.6
通讯作者：
Ogunshola, O. O.
中科院分区：
文献类型：
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作者：
Al Ahmad, A.;Gassmann, M.;Ogunshola, O. O.
血脑屏障（BBB）由星形胶质细胞和周细胞包围的特殊内皮细胞组成，在大脑稳态中发挥着至关重要的作用。许多脑血管疾病与血脑屏障破坏有关，缺氧 (O-2) 是导致其破坏的关键因素。我们研究了不同程度的 O-2 剥夺期间星形胶质细胞和周细胞对脑内皮细胞通透性和存活的影响。长时间暴露于 1% O-2 会导致屏障破坏，而暴露于 0.1% O-2 会显着加速破坏并诱导细胞死亡，这至少部分是通过 caspase-3 激活介导的。再充氧仅允许暴露于 1% O-2 的细胞重新建立屏障功能。值得注意的是，与星形胶质细胞和周细胞共培养可显着增强常氧条件下的屏障功能，并在 O-2 剥夺期间产生不同的反应。在 1% O-2 下，星形胶质细胞部分维持屏障完整性，而周细胞在短期内加速其破坏，只有在长期暴露后才产生积极作用。出乎意料的是，0.1% O-2 周细胞在保留屏障功能方面比星形胶质细胞更有效，尽管两种细胞提供的保护都涉及 caspase-3 途径的抑制。此外，自分泌和旁分泌 VEGF 信号通路的细胞特异性调节也在一定程度上导致了屏障功能的差异调节。我们的数据表明，神经血管单元内的细胞串扰对于维持屏障完整性至关重要，并且周细胞（而不是星形胶质细胞）在严重和长期的 O-2 剥夺期间发挥着重要作用。
The blood-brain barrier (BBB), consisting of specialized endothelial cells surrounded by astrocytes and pericytes, plays a crucial role in brain homeostasis. Many cerebrovascular diseases are associated with BBB breakdown and oxygen (O-2) deprivation constitutes a critical factor that onsets its disruption. We investigated the impact of astrocytes and pericytes on brain endothelial cell permeability and survival during different degrees O-2 deprivation. Prolonged exposure to 1% O-2 caused barrier breakdown and exposure to 0.1% O-2 dramatically accelerated disruption and induced cell death, mediated at least in part via caspase-3 activation. Reoxygenation allowed only cells exposed to 1% O-2 to re-establish barrier function. Notably co-culture with astrocytes and pericytes substantially enhanced barrier function under normoxic conditions, and produced differential responses during O-2 deprivation. At 1% O-2 astrocytes partially maintained barrier integrity whereas pericytes accelerated its disruption in the short-term, having positive effects only after prolonged exposure. Unexpectedly, at 0.1% O-2 pericytes were more effective than astrocytes in preserving barrier function although the protection afforded by both cells involved inhibition of caspase-3 pathways. Furthermore, cell-specific regulation of auto-and paracrine VEGF signaling pathways were also in part responsible for the differential modulation of barrier function. Our data suggests that cellular cross-talk within the neurovascular unit is crucial for preservation of barrier integrity and that pericytes, not astrocytes, play a significant role during severe and prolonged O-2 deprivation.