Braun Ramona, Klein Rebecca, Walter Helene Luise, Ohren Maurice, Freudenmacher Lars, Getachew Kaleab, Ladwig Anne, Luelling Joachim, Neumaier Bernd, Endepols Heike, Graf Rudolf, Hoehn Mathias, Fink Gereon Rudolf, Schroeter Michael, Rueger Maria Adele
Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931 Cologne, Germany.
Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
Exp Neurol. 2016 May;279:127-136. doi: 10.1016/j.expneurol.2016.02.018. Epub 2016 Feb 26.
Clinical data suggest that transcranial direct current stimulation (tDCS) may be used to facilitate rehabilitation after stroke. However, data are inconsistent and the neurobiological mechanisms underlying tDCS remain poorly explored, impeding its implementation into clinical routine. In the healthy rat brain, tDCS affects neural stem cells (NSC) and microglia. We here investigated whether tDCS applied after stroke also beneficially affects these cells, which are known to be involved in regeneration and repair.
Focal cerebral ischemia was induced in rats by transient occlusion of the middle cerebral artery. Twenty-eight animals with comparable infarcts, as judged by magnetic resonance imaging, were randomized to receive a multi-session paradigm of either cathodal, anodal, or sham tDCS. Behaviorally, recovery of motor function was assessed by Catwalk. Proliferation in the NSC niches was monitored by Positron-Emission-Tomography (PET) employing the radiotracer 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT). Microglia activation was depicted with [(11)C]PK11195-PET. In addition, immunohistochemical analyses were used to quantify neuroblasts, oligodendrocyte precursors, and activation and polarization of microglia.
Anodal and cathodal tDCS both accelerated functional recovery, though affecting different aspects of motor function. Likewise, tDCS induced neurogenesis independently of polarity, while only cathodal tDCS recruited oligodendrocyte precursors towards the lesion. Moreover, cathodal stimulation preferably supported M1-polarization of microglia.
TDCS acts through multifaceted mechanisms that far exceed its primary neurophysiological effects, encompassing proliferation and migration of stem cells, their neuronal differentiation, and modulation of microglia responses.
临床数据表明，经颅直流电刺激（tDCS）可用于促进中风后的康复。然而，数据并不一致，tDCS潜在的神经生物学机制仍未得到充分探索，这阻碍了其在临床常规治疗中的应用。在健康大鼠大脑中，tDCS会影响神经干细胞（NSC）和小胶质细胞。我们在此研究中风后应用tDCS是否也会对这些已知参与再生和修复的细胞产生有益影响。
通过短暂阻断大脑中动脉在大鼠中诱导局灶性脑缺血。根据磁共振成像判断，将28只梗死灶相当的动物随机分为接受阴极、阳极或假tDCS的多疗程模式。在行为上，通过Catwalk评估运动功能的恢复情况。使用放射性示踪剂3'-脱氧-3'-[(18)F]氟-L-胸腺嘧啶核苷（[(18)F]FLT），通过正电子发射断层扫描（PET）监测NSC龛中的增殖情况。用[(11)C]PK11195-PET描绘小胶质细胞的激活情况。此外，免疫组织化学分析用于量化神经母细胞、少突胶质细胞前体以及小胶质细胞的激活和极化情况。
阳极和阴极tDCS均加速了功能恢复，尽管影响运动功能的不同方面。同样，tDCS诱导神经发生与极性无关，而只有阴极tDCS将少突胶质细胞前体募集到损伤部位。此外，阴极刺激更有利于支持小胶质细胞的M1极化。
tDCS通过多方面机制发挥作用，这些机制远远超出其主要的神经生理效应，包括干细胞的增殖和迁移、它们的神经元分化以及小胶质细胞反应的调节。
