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Effects of Toxoplasma gondii infection on the function and integrity of human cerebrovascular endothelial cells and the influence of verapamil treatment in vitro.
Brain Research ( IF 2.7 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.brainres.2020.147002
M S R Harun 1 , Victoria Marsh 2 , Nashwa A Elsaied 2 , Kevin F Webb 3 , Hany M Elsheikha 2
Affiliation  

Toxoplasma gondii can cause parasitic encephalitis, a life-threatening infection predominately occurs in immunocompromised individuals. T. gondii has the ability to invade the brain, but the mechanisms by which this parasite crosses the blood-brain-barrier (BBB) to cause brain damage remain incompletely understood. The present study reports the structural and functional changes associated with infection and replication of T. gondii within human cerebrovascular endothelial cells (ECs) in vitro. Our results indicated that exposure of ECs to T. gondii had adverse impact on the function and integrity of the ECs - through reduced viability and increased monolayer permeability as well as altered expression of cytokine and tight junction genes. The P-glycoprotein (P-gp) inhibitor verapamil was found to be effective in inhibiting T. gondii crossing the ECs in a dose-dependent manner. The present study showed that T. gondii can compromise several functions of human cerebrovascular endothelial cells and demonstrated the ability of verapamil to inhibit T. gondii crossing of the BBB-ECs in vitro.



中文翻译:

弓形虫感染对人脑血管内皮细胞功能和完整性的影响及体外维拉帕米治疗的影响。

弓形虫可引起寄生性脑炎,一种危及生命的感染主要发生在免疫功能低下的个体中。弓形虫具有侵入大脑的能力,但这种寄生虫穿过血脑屏障 (BBB) 导致脑损伤的机制仍不完全清楚。本研究报告了与体外人脑血管内皮细胞 (EC) 内弓形虫感染和复制相关的结构和功能变化。我们的结果表明,ECs 暴露于弓形虫通过降低活力和增加单层渗透性以及改变细胞因子和紧密连接基因的表达,对 EC 的功能和完整性产生不利影响。发现 P-糖蛋白 (P-gp) 抑制剂维拉帕米可有效抑制弓形虫以剂量依赖性方式穿过 EC。本研究表明,弓形虫可以损害人脑血管内皮细胞的多种功能,并证明了维拉帕米在体外抑制弓形虫穿过 BBB-EC的能力

更新日期:2020-06-24
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