title: Transcranial direct current stimulation accelerates recovery of function, induces neurogenesis and recruits oligodendrocyte precursors in a rat model of stroke.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ramona
authors.initials: R
authors.lastname: Braun
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Helene Luise
authors.initials: HL
authors.lastname: Walter
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Maurice
authors.initials: M
authors.lastname: Ohren
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Freudenmacher
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Kaleab
authors.initials: K
authors.lastname: Getachew
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Ladwig
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Luelling
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany; Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Department of Nuclear Medicine, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Endepols
authors.affiliation: Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.affiliation: Max Planck Institute for Metabolism Research, Gleueler Str. 50, 50931 Cologne, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Department of Neurology, University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, 52425 Juelich, Germany.
authors.forename: Gereon Rudolf
authors.initials: GR
authors.lastname: Fink
authors.affiliation: 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; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, 52425 Juelich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.affiliation: 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; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, 52425 Juelich, Germany. Electronic address: adele.rueger@uk-koeln.de.
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Rueger
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D004566:Electrodes; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008262:Macrophage Activation; D008297:Male; D017628:Microglia; D009416:Nerve Regeneration; D058953:Neural Stem Cells; D055495:Neurogenesis; D009836:Oligodendroglia; D049268:Positron-Emission Tomography; D011597:Psychomotor Performance; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D020521:Stroke / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D065908:Transcranial Direct Current Stimulation / Q000379:methods*
keywords: Catwalk; Microglia polarization; Neurogenesis; Oligodendrocyte precursors; [(11)C]PK11195-PET; [(18)F]FLT-PET