Modulation of blood-brain-barrier (BBB) permeability by tDCS relevant electric fi

描述（由申请人提供）：经颅直流电刺激（tDCS）是一种非侵入性电刺激技术，用于广泛的医学和性能适应症。了解tDCS的细胞机制将增加正在进行的研究的严谨性，并为剂量优化提供合理的基础。先前的机制研究只集中在直流电刺激（DCS）下神经元膜的直接极化。我们建议测试tDCS直接和短暂调节血脑屏障（BBB）功能的假设，而血脑屏障功能反过来又会调节神经元活动。我们的方法是使用最先进的动物和组织模型和表征来确定一类新的细胞靶点，即内皮细胞，是否对DCS有反应。这些方法包括DCS期间和之后血管通透性的多光子经颅定量成像以及内皮屏障的分子和一般反应的分离。因为了解刺激的每一个细胞靶点是一个全面的机制所必需的，所以tDCS对血脑屏障的调节，结合直接的神经元效应，是研究的新颖和关键。本研究将首次确定tDCS直接血脑屏障作用的可行性，并定量预测这些变化对神经元功能的影响。

DESCRIPTION (provided by applicant): Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Understanding the cellular mechanisms of tDCS will increase the rigor of ongoing studies and provide a rational basis for dose optimization. Prior mechanistic studies have focused exclusively on direct polarization of neuronal membranes by direct current stimulation (DCS). We propose to test the hypothesis that tDCS directly and transiently modulates blood-brain-barrier (BBB) function, which in turn would modulate neuronal activity. Our approach is to use state-of-the-art animal and tissue models and characterization to determine if a new-class of cellular targets, namely endothelial cells, respond to DCS. These approaches including multi-photon transcranial quantitative imaging of vascular permeability during and after DCS and isolation of molecular and generic responses of endothelial barriers. Because understanding every cellular target of stimulation is required for a comprehensive mechanism, the modulation of BBB by tDCS, in conjunction with direct neuronal effects, is novel and critical to research. This study will be the first to establish the feasibility of direct BBB actions by tDCS as well as quantitatively predict the impact of these changes on neuronal function.