title: Multi-session transcranial direct current stimulation (tDCS) elicits inflammatory and regenerative processes in the rat brain.
abstract: Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16) were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min). Bromodeoxyuridine (BrdU) was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC). Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany. adele.rueger@uk-koeln.de
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Rueger
authors.forename: Meike Hedwig
authors.initials: MH
authors.lastname: Keuters
authors.forename: Maureen
authors.initials: M
authors.lastname: Walberer
authors.forename: Ramona
authors.initials: R
authors.lastname: Braun
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klein
authors.forename: Roland
authors.initials: R
authors.lastname: Sparing
authors.forename: Gereon Rudolf
authors.initials: GR
authors.lastname: Fink
authors.forename: Rudolf
authors.initials: R
authors.lastname: Graf
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D002452:Cell Count; D004553:Electric Conductivity; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods*; D004566:Electrodes; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000473:pathology; D058953:Neural Stem Cells / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012886:Skull; D020521:Stroke / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy