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In Vivo Modulation of the Blood-Brain Barrier Permeability by Transcranial Direct Current Stimulation (tDCS).
Annals of Biomedical Engineering ( IF 3.8 ) Pub Date : 2020-01-08 , DOI: 10.1007/s10439-020-02447-7
Da Wi Shin 1 , Jie Fan 1 , Eric Luu 1 , Wasem Khalid 1 , Yifan Xia 1 , Niranjan Khadka 1 , Marom Bikson 1 , Bingmei M Fu 1
Affiliation  

tDCS has been used to treat various brain disorders and its mechanism of action (MoA) was found to be neuronal polarization. Since the blood-brain barrier (BBB) tightly regulates the neuronal microenvironment, we hypothesized that another MoA of tDCS is direct vascular activation by modulating the BBB structures to increase its permeability (P). To test this hypothesis, we used high resolution multiphoton microscopy to determine P of the cerebral microvessels in rat brain. We found that 20 min 0.1-1 mA tDCS transiently increases P to a small solute, sodium fluorescein (MW 376) and to a large solute, Dextran-70k, with a much higher increase in P to the large solute. By pretreating the vessel with a nitric oxide synthase inhibitor, we revealed that the tDCS-induced increase in P is NO dependent. A transport model for the BBB was further employed to predict the structural changes by the tDCS. Comparing model predictions with the measured data suggests that tDCS increases P by temporarily disrupting the structural components forming the paracellular pathway of the BBB. That the transient and reversible increase in the BBB permeability also suggests new applications of tDCS such as a non-invasive approach for brain drug delivery through the BBB.

中文翻译:

通过经颅直流电刺激(tDCS)体内调节血脑屏障通透性。

tDCS已用于治疗各种脑部疾病,其作用机制(MoA)被发现是神经元极化。由于血脑屏障(BBB)紧密调节神经元微环境,我们假设tDCS的另一个MoA是通过调节BBB结构以增加其通透性(P)来直接激活血管。为了验证这一假设,我们使用高分辨率多光子显微镜确定大鼠大脑中脑微血管的P。我们发现20分钟的0.1-1 mA tDCS将P瞬时增加到小的溶质荧光素钠(MW 376)和大溶质Dextran-70k,而P增加到大溶质更高。通过用一氧化氮合酶抑制剂预处理血管,我们发现tDCS诱导的P升高是NO依赖性的。BDC的运输模型进一步被tDCS预测结构变化。将模型预测与测量数据进行比较表明,tDCS通过暂时破坏形成BBB旁细胞途径的结构成分来增加P。BBB通透性的瞬时和可逆增加也表明tDCS的新应用,例如通过BBB进行脑部药物输送的非侵入性方法。
更新日期:2020-01-08
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