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A microfluidic model of the blood-brain barrier to study permeabilization by pulsed electric fields

机译：血脑屏屏障的微流体模型，脉冲电场研究渗透

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摘要

Pulsed electric fields interact with the blood-brain barrier (BBB) and have been shown to increase the BBB permeability under some pulsing regimes. Pulsed electric fields may enhance drug delivery to the brain by disrupting the integrity of the BBB and allowing otherwise impermeable drugs to reach target areas. Microfluidic, in vitro models offer an alternative platform for exploring the impact of pulsed electric fields on the BBB because they create physiologically relevant microenvironments and eliminate the confounding variables of animal studies. We developed a microfluidic platform for real-time measurement of BBB permeability pre-and post-treatment with pulsed electric fields. Permeability is measured optically by the diffusion of fluorescent tracers across a monolayer of human cerebral microcapillary endothelial cells (hCMECs) cultured on a permeable membrane. We found that this device is able to capture real-time permeability of hCMEC monolayers for both reversible and irreversible electroporation pulsing regimes. Furthermore, preliminary testing of deep brain stimulation pulsing regimes reveals possible impacts on BBB integrity. This device will enable future studies of pulsed electric field regimes for improved understanding of BBB permeabilization.
机译：脉冲电场与血脑屏障（BBB）相互作用，并且已被证明在一些脉冲制度下增加BBB渗透率。脉冲电场可以通过破坏BBB的完整性并使其他药物达到目标区域来增强对大脑的药物输送。微流体，体外模型提供了探索BBB上脉冲电场对BBB的影响的替代平台，因为它们会产生生理相关的微环境并消除动物研究的混杂变量。我们开发了一种微流体平台，用于使用脉冲电场预先处理的BBB渗透性的实时测量。通过在渗透膜上培养的单层培养的人脑微小毛细管内皮细胞（HCMEC）的单层的荧光示踪剂的扩散，光学性地测量渗透性。我们发现该设备能够捕获HCMEC单层的实时渗透性，用于可逆和不可逆的电穿孔脉冲制度。此外，对深脑刺激脉冲制度的初步测试揭示了对BBB完整性的可能影响。该装置将使脉冲电场制度的未来研究能够提高对BBB渗透性的理解。

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  • 来源
    《RSC Advances》 |2017年第68期|共8页
  • 作者

    Bonakdar M.; Graybill P. M.; Davalos R. V.;

  • 作者单位

    Virginia Polytech Inst &

    State Univ Dept Biomed Engn &

    Mech Bioelectromech Syst Lab Blacksburg VA 24061 USA;

    Virginia Polytech Inst &

    State Univ Dept Biomed Engn &

    Mech Bioelectromech Syst Lab Blacksburg VA 24061 USA;

    Virginia Polytech Inst &

    State Univ Dept Biomed Engn &

    Mech Bioelectromech Syst Lab Blacksburg VA 24061 USA;

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  • 正文语种 eng
  • 中图分类 化学;
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