Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model

Fabiola Paciello, Marco Rinaudo, Maria Vittoria Podda, Claudio Grassi, Saviana Antonella Barbati, Agnese Re, Francesca Miraglia, Paolo Maria Rossini, Valentina Longo, Maria Bolla, Francesca Alù, Martina Gaia Di Donna, Fabrizio Vecchio

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review


BACKGROUND: More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. METHODS: Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. RESULTS: Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulindependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCSpromoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. CONCLUSIONS: The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.
Lingua originaleEnglish
pagine (da-a)1746-1758
Numero di pagine13
Stato di pubblicazionePubblicato - 2022


  • biomarker
  • Transcranial Direct Current Stimulation
  • forelimb
  • ischemia
  • motor cortex
  • personalized medicine
  • transcranial direct current stimulation
  • Animals
  • Brain-Derived Neurotrophic Factor
  • Disease Models, Animal
  • Humans
  • Mice
  • Neuronal Plasticity
  • Motor Cortex
  • Stroke
  • brain-derived neurotrophic factor


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