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Endothelial progenitor cell transplantation restores vascular injury in mice after whole-brain irradiation.
Brain Research ( IF 2.9 ) Pub Date : 2020-07-02 , DOI: 10.1016/j.brainres.2020.147005
Xurui Huang 1 , Minping Li 1 , Dongxiao Zhou 1 , Zhezhi Deng 1 , Junjie Guo 1 , Haiwei Huang 1
Affiliation  

Vascular damage plays an important role in the pathogenesis of radiation-induced brain injury (RBI). Endothelial progenitor cells (EPCs) are responsible for maintaining and repairing endothelial function, and have become a promising method for the treatment of cerebrovascular diseases. However, whether EPC transplantation plays a protective role in RBI has not been fully elucidated. Therefore, the present study investigated the effects of bone marrow-derived EPC transplantation in a whole-brain irradiation (WBI) mouse model. Mice were divided into the three groups: control group, irradiation group and EPCs group. Phosphate buffered saline or EPCs were intravenously injected into mice one week after irradiation, and brains were analyzed eight weeks after injection. Flow cytometry demonstrated that irradiation led to a significant reduction in the peripheral blood EPC count; however, EPC transplantation led to a significant increase in the circulating EPCs. Intravital two-photon imaging and western blotting demonstrated that EPC transplantation reversed the effects of irradiation by decreasing blood–brain barrier permeability and increasing the expression of tight junction proteins in the brain. Additionally, immunofluorescence staining revealed that the brain microvascular density was higher in the EPCs group than the irradiation group. Therefore, EPC transplantation may restore damage caused by WBI to the blood–brain barrier, tight junctions, and cerebral capillary density. These results highlight the potential beneficial effects of EPC transplantation on vascular damage induced by RBI.



中文翻译:

内皮祖细胞移植可恢复全脑照射后小鼠的血管损伤。

血管损伤在辐射性脑损伤 (RBI) 的发病机制中起重要作用。内皮祖细胞(EPCs)负责维持和修复内皮功能,已成为治疗脑血管疾病的一种很有前景的方法。然而,EPC移植是否在RBI中起保护作用尚未完全阐明。因此,本研究调查了骨髓来源的 EPC 移植在全脑照射 (WBI) 小鼠模型中的影响。将小鼠分为三组:对照组、照射组和EPCs组。照射后一周将磷酸盐缓冲盐水或 EPC 静脉注射到小鼠体内,并在注射后八周对大脑进行分析。流式细胞术表明,辐射导致外周血 EPC 计数显着减少;然而,EPC 移植导致循环 EPC 显着增加。活体双光子成像和蛋白质印迹证明 EPC 移植通过降低血脑屏障通透性和增加大脑中紧密连接蛋白的表达来逆转辐射的影响。此外,免疫荧光染色显示,EPCs 组的脑微血管密度高于照射组。因此,EPC 移植可以恢复 WBI 对血脑屏障、紧密连接和脑毛细血管密度造成的损伤。这些结果突出了 EPC 移植对 RBI 诱导的血管损伤的潜在有益影响。

更新日期:2020-07-08
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