Liebetanz David, Koch Reinhard, Mayenfels Susanne, König Fatima, Paulus Walter, Nitsche Michael A
Department of Clinical Neurophysiology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37099 Göttingen, Germany.
Clin Neurophysiol. 2009 Jun;120(6):1161-7. doi: 10.1016/j.clinph.2009.01.022. Epub 2009 Apr 28.
The aim of this rat study was to investigate the safety limits of extended transcranial direct current stimulation (tDCS). tDCS may be of therapeutic value in several neuro-psychiatric disorders. For its clinical applicability, however, more stable effects are required, which may be induced by intensified stimulations.
Fifty-eight rats received single cathodal stimulations at 1-1000 microA for up to 270 min through an epicranial electrode (3.5 mm(2)). Histological evaluation (H&E) was performed 48 h later. A threshold estimate was calculated from volumes of DC-induced lesions.
Brain lesions occurred at a current density of 142.9 A/m(2) for durations greater than 10 min. For current densities between 142.9 and 285.7 A/m(2), lesion size increased linearly with charge density; with a calculated zero lesion size intercept of 52,400 C/m(2). Brains stimulated below either this current density or charge density threshold, including stimulations over 5 consecutive days, were morphologically intact.
The experimentally determined threshold estimate is two orders of magnitude higher than the charge density currently applied in humans (171-480 C/m(2)). In relation to transcranial DC stimulation in humans the rat epicranial electrode montage may provide for an additional safety margin.
Although these results cannot be directly transferred to humans, they encourage the development intensified tDCS protocols. Further animal studies are required, before such protocols can be applied in humans.
本大鼠研究旨在探究延长经颅直流电刺激（tDCS）的安全限度。tDCS在多种神经精神疾病中可能具有治疗价值。然而，就其临床适用性而言，需要更稳定的效果，这可能通过强化刺激来诱导。
58只大鼠通过头皮电极（3.5平方毫米）接受1 - 1000微安的单次阴极刺激，持续时间长达270分钟。48小时后进行组织学评估（苏木精-伊红染色）。根据直流电诱导损伤的体积计算阈值估计值。
当电流密度为142.9安/平方米且持续时间超过10分钟时出现脑损伤。对于142.9至285.7安/平方米之间的电流密度，损伤大小随电荷密度呈线性增加；计算得出的零损伤大小截距为52,400库仑/平方米。在该电流密度或电荷密度阈值以下进行刺激，包括连续5天的刺激，大脑形态均保持完整。
实验确定的阈值估计值比目前人类应用的电荷密度（171 - 480库仑/平方米）高两个数量级。对于人类经颅直流电刺激，大鼠头皮电极设置可能提供额外的安全边际。
尽管这些结果不能直接应用于人类，但它们鼓励开发强化tDCS方案。在将此类方案应用于人类之前，还需要进一步的动物研究。
