VEGI attenuates the inflammatory injury and disruption of blood-brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
VEGI attenuates the inflammatory injury and disruption of blood-brain barrier partly by suppressing the TLR4/NF-κB signaling pathway in experimental traumatic brain injury
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VEGI 通过抑制实验性脑外伤中的 TLR4/NF-κ B 信号通路来减轻炎症损伤和血脑屏障破坏
DOI：
10.1016/j.brainres.2015.04.035
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发表时间：
2015-10-05
期刊：
影响因子：
2.9
通讯作者：
Zhang, Jianning
中科院分区：
文献类型：
--
作者：
Gao, Weiwei;Zhao, Zilong;Zhang, Jianning
急性创伤性脑损伤（TBI）易引起炎症反应过度激活和血脑屏障（BBB）破坏，并伴有长期的认知和行为功能障碍。血管内皮细胞生长抑制因子（VEGI）作为一种特异性的血管生成抑制因子，通过诱导增殖的内皮细胞凋亡而被应用于多种疾病，尤其是肿瘤。但在脑损伤方面的研究却很少。因此，在本研究中，我们研究了VEGF诱导的小鼠TBI模型CNS损伤后神经保护作用及其机制。我们证明VEGI治疗减少了挫伤脑组织的损失、炎性细胞（MPO+）的渗透和小胶质细胞（Iba-1（+））的活化。该治疗上调了紧密连接蛋白（CLN 5、ZO-1和OCLN）（其对于血脑屏障（BB B）的完整性至关重要）、B细胞淋巴瘤2（Bcl-2）细胞存活因子，同时下调了TLR 4、NF-κ B和炎性细胞因子（IL-1 β、TNF-α、iNOS）的表达。治疗还降低了反应性星形胶质细胞（GFAP（+））和VEGF的表达，并降低了伊文思蓝（EB）的渗透性。提示VEGF治疗可减轻创伤后过度炎症反应，维持血管稳定，减轻继发性脑损伤。(C)2015年由Elsevier B. V.出版
Acute traumatic brain injury (TBI) tends to cause the over-activation of inflammatory response and disruption of blood brain barrier (BBB), associating with long-term cognitive and behavioral dysfunction. Vascular endothelial growth inhibitor (VEGI), as a suppressor in the angiogenesis specifically by inducing apoptosis in proliferating endothelial cells, has been applied to different diseases, especially the tumors. But rare study had been done in the field of brain injury. So in this study, we investigated the effects and mechanisms associated with VEGI-induced neuroprotection following CNS injury in mice TBI models. We demonstrated that the VEGI treatment reduced the contusion brain tissue loss, the permeation of inflammatory cells (MPO+) and the activation of microglia (Iba-1(+)). The treatment upregulated the tight junction proteins (CLN5, ZO-1 and OCLN), which are vital importance for the integrity of the blood brain barrier (BBB), the B-cell lymphoma 2 (Bcl-2) cell survival factors, while down-regulated the expression of TLR4, NF-kappa B and inflammatory cytokines (IL-1 beta, TNF-alpha, iNOS). The treatment also decreased the expression of reactive astrocytes (GFAP(+)), as well as the VEGF, and lowered the permeability of Evens Blue (EB). These findings suggested that the VEGI-treatment could alleviate the post-traumatic excessive inflammatory response, and maintain the stability of blood vessels, remitting the secondary brain damage. (C) 2015 Published by Elsevier B.V.