Inhibition of stress fiber formation preserves blood-brain barrier after intracerebral hemorrhage in mice
Inhibition of stress fiber formation preserves blood-brain barrier after intracerebral hemorrhage in mice
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DOI：
10.1177/0271678x16679169
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发表时间：
2018-01-01
影响因子：
6.3
通讯作者：
Tang, Jiping
中科院分区：
文献类型：
--
作者：
Manaenko, Anatol;Yang, Peng;Tang, Jiping
脑出血 (ICH) 是所有中风中最致命的亚型。血脑屏障 (BBB) 破坏导致的脑水肿是脑出血后最危及生命的事件。病理生理条件激活内皮细胞（BBB 的组成部分之一），诱导肌动蛋白细胞骨架重排。激活后，球状肌动蛋白组装成丝状肌动蛋白，从而形成收缩性肌动蛋白束、应力纤维。应力纤维的收缩导致内皮细胞之间形成细胞间隙，增加血脑屏障的通透性。在本研究中，我们研究了 ICH 对 CD1 小鼠应激纤维形成的影响。我们假设 ICH 诱导的应激纤维形成是由 PDGFR-β 的激活触发的，并由 cortactin/RhoA/LIMK 通路介导。我们证明 ICH 会诱导应力纤维的形成。此外，我们证明抑制PDGFR-β及其下游可减少应激纤维的数量，保留BBB，从而改善ICH后小鼠的脑水肿和神经功能。
Intracerebral hemorrhage (ICH) represents the deadliest subtype of all strokes. The development of brain edema, a consequence of blood-brain barrier (BBB) disruption, is the most life-threatening event after ICH. Pathophysiological conditions activate the endothelium, one of the components of BBB, inducing rearrangement of the actin cytoskeleton. Upon activation, globular actin assembles into a filamentous actin resulting in the formation of contractile actin bundles, stress fibers. The contraction of stress fibers leads to the formation of intercellular gaps between endothelial cells increasing the permeability of BBB. In the present study, we investigated the effect of ICH on stress fiber formation in CD1 mice. We hypothesized that ICH-induced formation of stress fiber is triggered by the activation of PDGFR-beta and mediated by the cortactin/RhoA/LIMK pathway. We demonstrated that ICH induces formation of stress fibers. Furthermore, we demonstrated that the inhibition of PDGFR-beta and its downstream reduced the number of stress fibers, preserving BBB and resulting in the amelioration of brain edema and improvement of neurological functions in mice after ICH.