Transcranial Direct Current Stimulation Accelerates Recovery of Function, Induces Neurogenesis and Recruits Oligodendrocyte Precursors in a Rat Model of Stroke

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.