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

通过 tDCS 相关电刺激调节血脑屏障 (BBB) 通透性

• 批准号: 8702690
• 负责人: MAROM BIKSON
• 金额: $ 22.95万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702690
• 关键词: Animal Model; Biological Models; Blood - brain barrier anatomy; Blood Vessels; Brain; Cell Culture Techniques; Clinical Trials Design; Computer Simulation; Development; Dose; Electric Stimulation; Electrodes; Endothelial Cells; Exploratory/Developmental Grant; Faculty; Funding; Gene Expression; Generic Drugs; Grant; Head; Image; Imagery; Immunohistochemistry; In Vitro; Medical; Membrane; Methods; Microscopic; Microscopy; Modeling; Molecular; Molecular Analysis; Neurons; Pathway interactions; Performance; Permeability; Physiological; Publications; Publishing; Research; Research Personnel; Resolution; Safety; Skin; Source; Specificity; System; Techniques; Testing; Tight Junctions; Time; Tissue Model; United States National Institutes of Health; Vascular Permeabilities; base; behavior observation; brain tissue; cellular targeting; direct application; follow-up; imaging modality; improved; in vitro Model; in vivo; innovation; multi-photon; neuroregulation; novel; public health relevance; response; signal processing; square foot; submicron; tool

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.

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，用于广泛的医疗和性能适应症。 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。 先前的机制研究仅集中在通过直流电刺激（DCS）的神经元膜的直接极化上。 我们建议测试的假设，tDCS直接和瞬时调节血脑屏障（BBB）的功能，这反过来又会调节神经元的活动。 我们的方法是使用最先进的动物和组织模型和表征，以确定是否一类新的细胞靶点，即内皮细胞，响应DCS。 这些方法包括DCS期间和之后的血管通透性的多光子经颅定量成像和内皮屏障的分子和一般反应的分离。 由于了解刺激的每个细胞靶点是全面机制所必需的，因此tDCS对BBB的调节与直接的神经元效应结合在一起是新颖的，对研究至关重要。 这项研究将是第一个建立tDCS直接BBB作用的可行性，以及定量预测这些变化对神经元功能的影响。