Transcranial-Direct-Current-Stimulation Accelerates Motor Recovery After Cortical Infarction in Mice: The Interplay of Structural Cellular Responses and Functional Recovery

Abstract

Background Transcranial direct current stimulation (tDCS) promotes recovery after stroke in humans. The underlying mechanisms, however, remain to be elucidated. Animal models suggest tDCS effects on neuroinflammation, stem cell proliferation, neurogenesis, and neural plasticity. Objective In a longitudinal study, we employed tDCS in the subacute and chronic phase after experimental focal cerebral ischemia in mice to explore the relationship between functional recovery and cellular processes. Methods Mice received photothrombosis in the right motor cortex, verified by Magnetic Resonance Imaging. A composite neuroscore quantified subsequent functional deficits. Mice received tDCS daily: either 5 sessions from day 5 to 9, or 10 sessions with days 12 to 16 in addition. TDCS with anodal or cathodal polarity was compared to sham stimulation. Further imaging to assess proliferation and neuroinflammation was performed by immunohistochemistry at different time points and Positron Emission Tomography at the end of the observation time of 3 weeks. Results Cathodal tDCS at 198 kC/m2 (220 A/m2) between days 5 and 9 accelerated functional recovery, increased neurogenesis, decreased microglial activation, and mitigated CD16/32-expression associated with M1-phenotype. Anodal tDCS exerted similar effects on neurogenesis and microglial polarization but not on recovery of function or microglial activation. TDCS on days 12 to 16 after stroke did not induce any further effects, suggesting that the therapeutic time window was closed by then. Conclusion Overall, data suggest that non-invasive neuromodulation by tDCS impacts neurogenesis and microglial activation as critical cellular processes influencing functional recovery during the early phase of regeneration from focal cerebral ischemia.

Transcranial Direct Current Stimulation Reverses Stroke-Induced Network Alterations in Mice

“…Nevertheless, our data align with and extend to our recent findings, showing that 5 sessions of cathodal tDCS in a similar time window after stroke were sufficient to induce motor recovery after cortical stroke, while the additional 5 sessions in the second week after stroke added no further benefit. 35 Conversely, our data further revealed a connection between the extent of change in local clustering, presumably unaffected by tDCS, and the extent of motor recovery 14 days after stroke, by trend. This finding might cautiously suggest an overlap in network adaptations due to tDCS-augmented recovery (ie, a reversal in characteristic path length) and spontaneous recovery (ie, reversal increase in local clustering as a surrogate for neuroplasticity).…”

Brain complexity in stroke recovery after bihemispheric transcranial direct current stimulation in mice

“… 8 , 13-19 In animal model of stroke, it has been also shown that both anodal and cathodal tDCS stimulate neurogenesis and reduce microglia activation and polarization towards the neurotoxic M1-phenotype while stabilizing microglia polarization towards the neuroprotective M2-phenotype. 20 A reduced microglia activation in the perilesional region has also been proven following a very early application (i.e. 6 h after stroke) of cathodal tDCS in a mouse model of motor cortex stroke.…”

Mechanisms of transcranial direct current stimulation (tDCS) for pain in patients with fibromyalgia syndrome

“…Transcranial direct current stimulation may reduce FMS pain by modulating neuroinflammation, possibly achieved by stimulating brain immune cells, such as MCs and glial cells, to regulate pro-inflammatory cytokines release. Research showed tDCS can reduce the activation of microglia ( Walter et al, 2022 ), a type of essential glial cell in the neuroinflammatory process, thus decreasing the synthesis of TNF and other inflammatory mediators ( Guo et al, 2020 ).…”