A MULTIMODAL STRATEGY TO ENHANCE POST-STROKE MOTOR RECOVERY: TRANSCRANIAL DIRECT CURRENT STIMULATION MEETS BIOMIMETIC NANOPARTICLES

Persistent motor deficits represent a major cause of disability after ischemic stroke. Post-ischemic interhemispheric imbalance and immune activation interfere with circuit reorganization at multiple levels, limiting recovery and highlighting the need for multimodal therapeutic strategies to improve recovery. Here, we tested the efficacy of single and combined treatments consisting of pro-plastic transcranial direct current stimulation (tDCS) (doi:10.1161/STROKEAHA.121.034200) and biomimetic nanoparticles for the delivery of anti-inflammatory agents to stroke-injured neural tissue in a mouse model of photothrombotic stroke of the motor cortex. Nanoparticle formulations were screened in vitro for anti-inflammatory efficacy and cellular uptake, and the most effective formulation was selected for in vivo evaluation in combination with tDCS. Motor performance was assessed before stroke and at 1, 4, and 8 weeks using a battery of behavioural tests. Mice received bihemispheric tDCS or sham stimulation for three days, starting three days after stroke. tDCS-treated mice displayed sustained improvement in motor performance compared to sham-stimulated animals. Functional recovery was accompanied by reduced infarct volume and decreased microglial density within the perilesional region, indicating the attenuation of inflammatory response. Moreover, tDCS induced an increase in dendritic spine density at four weeks post-stroke and a sustained enhancement of long-term potentiation in the motor cortex for up to eight weeks, consistent with progressive and long-lasting synaptic plasticity. Preliminary data indicate that combined tDCS and biomimetic nanoparticle treatment yielded greater effects on functional recovery than nanoparticles alone, supporting possible synergistic/complementary effects.
Supported by the Italian Ministry of Health, Ricerca Finalizzata, RF-2021-12373484, CUP:C53C22001570001.