Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in rat.
Critical role of EphA4 in early brain injury after subarachnoid hemorrhage in rat.
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DOI：
10.1016/j.expneurol.2017.07.003
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发表时间：
2017-10
影响因子：
5.3
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Fan R;Enkhjargal B;Camara R;Yan F;Gong L;ShengtaoYao;Tang J;Chen Y;Zhang JH
早期脑损伤（EBI）是蛛网膜下腔出血（SAH）患者死亡的主要原因。Eph受体A4（EphA 4）与血脑屏障完整性和促凋亡相关。我们旨在研究EphA 4在SAH后EBI中的作用。179只成年雄性SD大鼠随机分为假手术组和SAH模型组。SAH后进行SAH分级、神经功能评分、伊文思蓝染色、脑含水量、死亡率、Fluoro-Jade染色、免疫荧光染色和western blot实验。EphA 4的小干扰RNA（siRNA）、重组Ephexin-1（rEphx-1）和法舒地尔（一种有效的ROCK 2抑制剂）用于干预以研究EphA 4对SAH后EBI的作用。SAH后EphA 4、Ephexin-1、RhoA和ROCK 2的表达显著增加。侧脑室注射EphA 4 siRNA敲低EphA 4可减少Evans蓝外渗，降低脑含水量，减轻SAH后神经行为功能障碍。此外，Ephexin-1、RhoA、ROCK 2和切割的caspase-3的表达降低。紧密连接蛋白增加，凋亡神经元死亡减少。EphA 4 siRNA的作用被rEphx-1消除。相比之下，法舒地尔消除了rEphx-1的作用。这些结果表明，EphA 4，一种新的和有前途的治疗靶点，通过Ephexin-1/ROCK 2途径加重SAH后的EBI。
Early brain injury (EBI) is reported as a primary cause of mortality in subarachnoid hemorrhage (SAH) patients. Eph receptor A4 (EphA4) has been associated with blood-brain barrier integrity and pro-apoptosis. We aimed to investigate a role of EphA4 in EBI after SAH. One hundred and seventy-nine male adult Sprague-Dawley rats were randomly divided into sham versus endovascular perforation model of SAH groups. SAH grade, neurological score, Evans blue dye extravasation, brain water content, mortality, Fluoro-Jade staining, immunofluorescence staining, and western blot experiments were performed after SAH. Small interfering RNA (siRNA) for EphA4, recombinant Ephexin-1 (rEphx-1), and Fasudil, a potent ROCK2 inhibitor, were used for intervention to study a role of EphA4 on EBI after SAH. The expression of EphA4, Ephexin-1, RhoA, and ROCK2 significantly increased after SAH. Knockdown of EphA4 using EphA4 siRNA injection intracerebroventricularly (i.c.v) reduced Evans blue extravasation, decreased brain water content, and alleviated neurobehavioral dysfunction after SAH. Additionally, the expression of Ephexin-1, RhoA, ROCK2 and cleaved caspase-3 were decreased. Tight junction proteins increased, and apoptotic neuron death decreased. The effects of EphA4 siRNA were abolished by rEphx-1. In contrast, Fasudil abolished the effects of rEphx-1. These results suggest that EphA4, a novel and promising target for treatment, exacerbates EBI through an Ephexin-1/ROCK2 pathway after SAH.
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影响因子：
6.9
作者：
Fujii, Mutsumi;Yan, Junhao;Rolland, William B.;Soejima, Yoshiteru;Caner, Basak;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
6.9
作者：
Chen, Qianwei;Zhang, Jianbo;Chen, Zhi
通讯作者：
Chen, Zhi
DOI：
10.1146/annurev-pharmtox-011112-140226
发表时间：
2015
影响因子：
12.5
作者：
Barquilla A;Pasquale EB
通讯作者：
Pasquale EB
影响因子：
8.3
作者：
Endo, Hidenori;Nito, Chikako;Chan, Pak H.
通讯作者：
Chan, Pak H.
影响因子：
6.3
作者：
Etminan, Nima;Di Vergouwen, Mervyn;Macdonald, R. Loch
通讯作者：
Macdonald, R. Loch