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Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

机译:经颅直流电刺激在体内短暂增加了血脑屏障的溶质通透性

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Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.
机译:经颅直流电刺激(tDCS)是一种无创的电刺激技术,已针对广泛的医学和功能适应症进行了研究。先前的研究仅专注于直接神经元极化,而我们的假设是tDCS直接调节内皮细胞,导致血脑屏障(BBB)通透性(P)的瞬时变化,这对于神经元活动非常有意义。为此,我们开发了最新的成像和动物模型,以在tDCS处理后将P定量化为各种大小的溶质。使用恒定电流刺激器对tDCS进行给药,以向大鼠的右额皮质(前2后约2 mm,矢状缝合线约2 mm)输送1mA电流,以获得与人类tDCS应用研究相似的生理结果。用恒定剂量的注射泵通过同侧颈动脉将1%BSA哺乳动物林格液中的荧光素钠(MW = 376)或FITC-右旋糖酐(20K和70K)注入大鼠(SD,250-300g)脑循环中速度〜3 ml / min。为了确定P,使用具有800-850 nm波长激光的多光子显微镜,用适当的微血管从感兴趣区域(ROI)拍摄图像,该微血管位于脑脊柱下方100-200微米。结果表明,tDCS预处理20分钟后10分钟,小溶质荧光素钠的P相对增加约8倍,中型(Dex-20k)和大(Dex-70k)溶质的P相对增加约35倍。处理后20分钟后,所有增加的渗透率都返回到对照中。结果证实了我们的假设。

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