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

机译:血脑屏障的微流模型研究脉冲电场的通透性

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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,并已显示在某些脉冲状态下可增加BBB的渗透性。脉冲电场可能会破坏BBB的完整性,并使不渗透的药物到达目标区域,从而增强药物向大脑的传递。微流体体外模型为探讨脉冲电场对血脑屏障的影响提供了另一个平台,因为它们创建了生理相关的微环境并消除了动物研究的混杂变量。我们开发了一种微流体平台,用于实时测量脉冲电场对BBB渗透性的预处理和后处理。通过荧光示踪剂在可渗透膜上培养的人脑微毛细血管内皮细胞(hCMEC)的单层扩散来光学测量通透性。我们发现该设备能够捕获可逆和不可逆电穿孔脉冲方案的hCMEC单层的实时渗透性。此外,对脑深部刺激脉冲方案的初步测试表明可能会对BBB完整性产生影响。该设备将使未来对脉冲电场机制的研究成为可能,以更好地了解BBB的通透性。

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