特定模式电针刺激通过调节 VEGFA 和 NF-κB 的紧密连接蛋白表达,在 MCAO/R 恢复期打开大鼠梗死边界区的血脑屏障。

IF 1.6 4区 医学 Q4 NEUROSCIENCES
Neuroreport Pub Date : 2024-11-06 Epub Date: 2024-09-19 DOI:10.1097/WNR.0000000000002098
Kecheng Qian, Mengyuan Dai, Lin Gan, Qinyu Ye, Xingying Wu, Tianyu Qian, Congcong Ma, Xianming Lin
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引用次数: 0

摘要

血脑屏障(BBB)严格限制了大多数外源性治疗药物进入大脑,这给包括缺血性中风治疗在内的难治性中枢疾病的药物治疗带来了巨大挑战。我们之前的研究表明,特定模式电针刺激(SMES)可以暂时打开BBB,但其机制尚不清楚。本研究通过体内和体外研究,探讨在大脑中动脉闭塞/再灌注恢复期,SMES是否能打开大鼠梗死边界区的BBB,以及这是否与p65或血管内皮生长因子A(VEGFA)调节紧密连接蛋白的表达有关。伊文思蓝、FITC-葡聚糖、小鼠神经生长因子(NGF)和跨内皮电阻值被用来评估 BBB 的通透性。此外,还利用微血管内皮细胞和星形胶质细胞进行体外研究。免疫荧光、免疫组织化学、Western 印迹和 ELISA 被用来评估相关蛋白质的表达。SMES能明显增加梗死边界区血管对伊文思蓝和NGF的通透性,并通过激活p-p65增加血管内皮生长因子的表达,从而减少紧密连接蛋白Occludin和ZO-1的表达。相应地,氧糖剥夺/复氧激活了体外星形胶质细胞中的 p-p65,并诱导其分泌 VEGFA。它们的条件培养基减少了 bEnd.3 细胞中 Occludin 的表达,并增加了 FITC-葡聚糖的通透性。SMES打开梗死边界区BBB的机制部分与其对p65、血管内皮生长因子和紧密连接蛋白的作用有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Specific mode electroacupuncture stimulation opens the blood-brain barrier of the infarcted border zone in rats during MCAO/R recovery via modulation of tight junction protein expression by VEGFA and NF-κB.

The blood-brain barrier (BBB) strictly limits the entry of most exogenous therapeutic drugs into the brain, which brings great challenges to the drug treatment of refractory central diseases, including the treatment of ischemic stroke. Our previous studies have shown that specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, but with the mechanisms largely unknown. This study explored whether SMES opens the BBB in the infarcted border zone of rats during middle cerebral artery occlusion/reperfusion recovery, and whether this is related to p65 or vascular endothelial growth factor A (VEGFA) modulation of tight junction protein expression through in vivo and in vitro studies. Evans blue, FITC-dextran, mouse-derived nerve growth factor (NGF), and transendothelial electrical resistance values were used to evaluate the permeability of the BBB. Additionally, microvascular endothelial cells and astrocytes were utilized for in vitro study. Immunofluorescence, immunohistochemistry, western blot, and ELISA were employed to assess related protein expression. SMES significantly increased vascular permeability for Evans blue and NGF in the infarcted border zone, and increased the expression of VEGFA by activating p-p65, thereby reducing the expression of tight junction proteins Occludin and ZO-1. Correspondingly, oxygen glucose deprivation/reoxygenation activated p-p65 in and induced VEGFA secretion from astrocytes in vitro. Their conditioned medium reduced the expression of Occludin in bEnd.3 cells and increased the permeability of FITC-dextran. The mechanism of SMES opening infarcted border zone BBB is partly related to its actions on p65, VEGFA, and tight junction proteins.

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来源期刊
Neuroreport
Neuroreport 医学-神经科学
CiteScore
3.20
自引率
0.00%
发文量
150
审稿时长
1 months
期刊介绍: NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.
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