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Cited by 151Transcranial Magnetic Stimulation StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Multi-Session Transcranial Direct Current Stimulation (tDCS) Elicits Inflammatory and Regenerative Processes in the Rat Brain

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Rueger, Maria Adele, Keuters, Meike Hedwig, Walberer, Maureen, Braun, Ramona, Klein, Rebecca, Sparing, Roland, Fink, Gereon Rudolf, Graf, Rudolf, Schroeter, Michael·2012·PLoS ONE
DOI 10.1371/journal.pone.0043776PMC PMC3425495
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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.

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Crossref · 10.1371/journal.pone.0043776

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Figures

Figure 1 Multi-session transcranial DCS with defined parameters does not cause a cerebral lesion or astrogliotic scar. (A) For multi-session tDCS, an epicranial electrode was mounted as schematically depicted (red circle). (B) H&E staining confirmed an intact cortex after multi-session focal tDCS, and (C) no astrogliotic scarring was detected by GFAP staining (scale bar = 1 mm).
Figure 1 Multi-session transcranial DCS with defined parameters does not cause a cerebral lesion or astrogliotic scar. (A) For multi-session tDCS, an epicranial electrode was mounted as schematically depicted (red circle). (B) H&E staining confirmed an intact cortex after multi-session focal tDCS, and (C) no astrogliotic scarring was detected by GFAP staining (scale bar = 1 mm).CC BY · PubMed Central
Figure 2 Multi-session tDCS activates cortical microglia. (A) The density of activated microglia identified by Iba1 immunoreactivity was increased in the cortex ipsilateral to multi-session tDCS (scale bar = 0.05 mm). (B) This increase in Iba1+ cells compared to the respective contralateral hemisphere was most pronounced early after cathodal tDCS, but also present after anodal stimulation; effects decreased with time (means ± SEM; *p = 0.05, **p<0.01).
Figure 2 Multi-session tDCS activates cortical microglia. (A) The density of activated microglia identified by Iba1 immunoreactivity was increased in the cortex ipsilateral to multi-session tDCS (scale bar = 0.05 mm). (B) This increase in Iba1+ cells compared to the respective contralateral hemisphere was most pronounced early after cathodal tDCS, but also present after anodal stimulation; effects decreased with time (means ± SEM; *p = 0.05, **p<0.01).CC BY · PubMed Central
Figure 3 Multi-session tDCS leads to ICAM1 upregulation. (A) ICAM1 immunoreactivity was increased in the ipsilateral hemisphere after multi-session cathodal or anodal tDCS, (scale bar = 0.2 mm). (B) ICAM1+ vessels trended to increase with time upon cathodal tDCS, while anodal tDCS caused only a transient increase (note that differences were not statistically significant; means ± SEM).
Figure 3 Multi-session tDCS leads to ICAM1 upregulation. (A) ICAM1 immunoreactivity was increased in the ipsilateral hemisphere after multi-session cathodal or anodal tDCS, (scale bar = 0.2 mm). (B) ICAM1+ vessels trended to increase with time upon cathodal tDCS, while anodal tDCS caused only a transient increase (note that differences were not statistically significant; means ± SEM).CC BY · PubMed Central
Figure 4 Cathodal tDCS increases the number of proliferating cells in the cortex. (A) After multi-session cathodal tDCS, the number of proliferating cells identified by BrdU-incorporation was increased in the ipsilateral hemisphere (scale bar = 0.5 mm). (B) This effect was only observed with cathodal stimulation. Anodal tDCS had no effect on proliferation in the cortex (means ± SEM; **p<0.01, *p<0.05).
Figure 4 Cathodal tDCS increases the number of proliferating cells in the cortex. (A) After multi-session cathodal tDCS, the number of proliferating cells identified by BrdU-incorporation was increased in the ipsilateral hemisphere (scale bar = 0.5 mm). (B) This effect was only observed with cathodal stimulation. Anodal tDCS had no effect on proliferation in the cortex (means ± SEM; **p<0.01, *p<0.05).CC BY · PubMed Central
Figure 5 Cathodal tDCS increases the number of Hes3-positive neural stem cells in the cortex. (A) The density of NSC identified by Hes3 immunoreactivity was increased in the cortex ipsilateral to multi-session tDCS (scale bar = 0.05 mm). (B) The number of Hes3-positive NSC increased in the ipsilateral hemisphere with the duration of cathodal tDCS (means ± SEM; *p<0.05).
Figure 5 Cathodal tDCS increases the number of Hes3-positive neural stem cells in the cortex. (A) The density of NSC identified by Hes3 immunoreactivity was increased in the cortex ipsilateral to multi-session tDCS (scale bar = 0.05 mm). (B) The number of Hes3-positive NSC increased in the ipsilateral hemisphere with the duration of cathodal tDCS (means ± SEM; *p<0.05).CC BY · PubMed Central

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Metadata

Authors
Rueger, M. A., Keuters, M. H., Walberer, M., Braun, R., Klein, R., Sparing, R., Fink, G. R., Graf, R., & Schroeter, M.
Affiliations
  • Max Planck Institute for Metabolism Research (DE)
  • University Hospital Cologne (DE)
  • Forschungszentrum Jülich (DE)
Corresponding author
Rueger, Maria Adele
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-08-22
Volume
7
Issue
8
Pages
e43776
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0043776
PMC
PMC3425495
OpenAlex
W2012307799
Cited by
151
References
46
Citations by year
2026: 4 · 2025: 10 · 2024: 7 · 2023: 5 · 2022: 20 · 2021: 16 · 2020: 28 · 2019: 9 · 2018: 6 · 2017: 16 · 2016: 11 · 2015: 9 · 2014: 7 · 2013: 3
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • JuSER (Forschungszentrum Jülich) (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Universität zu Köln
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
transcranial direct current stimulation, neuroinflammation, neural stem cells, microglial activation, cell migration, anodal stimulation, cathodal stimulation, adaptive immunity, ICAM-1, stroke recovery, neurogenesis, rat brain
MeSH terms
Animals, Brain, Cell Count, Electric Conductivity, Electrodes, Electric Stimulation Therapy, Inflammation, Male, Regeneration, Skull, Rats, Wistar, Microglia, Stroke, Rats, Adaptive Immunity, Neural Stem Cells

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