title: Transcranial direct current stimulation promotes the mobility of engrafted NSCs in the rat brain.
abstract: Transcranial direct current stimulation (tDCS) is used in numerous clinical studies and considered an effective and versatile add-on therapy in neurorehabilitation. To date, however, the underlying neurobiological mechanisms remain elusive. In a rat model of tDCS, we recently observed a polarity-dependent accumulation of endogenous neural stem cells (NSCs) in the stimulated cortex. Based upon these findings, we hypothesized that tDCS may exert a direct migratory effect on endogenous NSCs towards the stimulated cortex. Using noninvasive imaging, we here investigated whether tDCS may also cause a directed migration of engrafted NSCs. Murine NSCs were labeled with superparamagnetic particles of iron oxide (SPIOs) and implanted into rat striatum and corpus callosum. MRI was performed (i) immediately after implantation and (ii) after 10 tDCS sessions of anodal or cathodal polarity. Sham-stimulated rats served as control. Imaging results were validated ex vivo using immunohistochemistry. Overall migratory activity of NSCs almost doubled after anodal tDCS. However, no directed migration within the electric field (i.e. towards or away from the electrode) could be observed. Rather, an undirected outward migration from the center of the graft was detected. Xenograft transplantation induced a neuroinflammatory response that was significantly enhanced following cathodal tDCS. This inflammatory response did not impact negatively on the survival of implanted NSCs. Data suggest that anodal tDCS increases the undirected migratory activity of implanted NSCs. Since the electric field did not guide implanted NSCs over large distances, previously observed polarity-dependent accumulation of endogenous NSCs in the cortex might have originated from local proliferation. Results enhance our understanding of the neurobiological mechanisms underlying tDCS, and may thereby help to develop a targeted and sustainable application of tDCS in clinical practice.
authors.affiliation: Department of Neurology, University Hospital of Cologne, Cologne, Germany; In-vivo-NMR Laboratory, Max Planck Institute for Neurological Research, Cologne, Germany.
authors.forename: Meike Hedwig
authors.initials: MH
authors.lastname: Keuters
authors.forename: Markus
authors.initials: M
authors.lastname: Aswendt
authors.forename: Annette
authors.initials: A
authors.lastname: Tennstaedt
authors.forename: Dirk
authors.initials: D
authors.lastname: Wiedermann
authors.forename: Anton
authors.initials: A
authors.lastname: Pikhovych
authors.forename: Steffen
authors.initials: S
authors.lastname: Rotthues
authors.forename: Gereon Rudolf
authors.initials: GR
authors.lastname: Fink
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.forename: Mathias
authors.initials: M
authors.lastname: Hoehn
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Rueger
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004566:Electrodes; D007109:Immunity / Q000187:drug effects; D007150:Immunohistochemistry; D007501:Iron / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation*; D010587:Phagocytosis / Q000187:drug effects; D017208:Rats, Wistar; D065908:Transcranial Direct Current Stimulation
chemical_list: D007501:Iron
keywords: MRI; galvanotaxis; microglia; migration; neuroinflammation; phagocytes; superparamagnetic particles of iron oxide