TY - JOUR
T1 - Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model
AU - Longo, Valentina
AU - Barbati, Saviana Antonella
AU - Re, Agnese
AU - Paciello, Fabiola
AU - Bolla, Maria
AU - Rinaudo, Marco
AU - Miraglia, Francesca
AU - Alù, Francesca
AU - Di Donna, Martina Gaia
AU - Vecchio, Fabrizio
AU - Rossini, Paolo Maria
AU - Podda, Maria Vittoria
AU - Grassi, Claudio
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Animals
KW - Brain-Derived Neurotrophic Factor
KW - Disease Models, Animal
KW - Humans
KW - Mice
KW - Motor Cortex
KW - Neuronal Plasticity
KW - Stroke
KW - Transcranial Direct Current Stimulation
KW - biomarker
KW - brain-derived neurotrophic factor
KW - forelimb
KW - ischemia
KW - motor cortex
KW - personalized medicine
KW - transcranial direct current stimulation
KW - Animals
KW - Brain-Derived Neurotrophic Factor
KW - Disease Models, Animal
KW - Humans
KW - Mice
KW - Motor Cortex
KW - Neuronal Plasticity
KW - Stroke
KW - Transcranial Direct Current Stimulation
KW - biomarker
KW - brain-derived neurotrophic factor
KW - forelimb
KW - ischemia
KW - motor cortex
KW - personalized medicine
KW - transcranial direct current stimulation
UR - http://hdl.handle.net/10807/202593
U2 - 10.1161/STROKEAHA.121.034200
DO - 10.1161/STROKEAHA.121.034200
M3 - Article
SN - 0039-2499
VL - 53
SP - 1746
EP - 1758
JO - Stroke
JF - Stroke
ER -