Modified constraint-induced movement therapy improves functional recovery after ischemic stroke and its impacts on exosome-derived microRNAs

OBJECTIVE: To investigate whether modified constraint-induced movement therapy (mCIMT) improves brain function after stroke by increasing the concentrations of exosomes and microRNA. METHODS: Blood samples from 16 stroke patients (mCIMT group N=8, control group N=8) were analyzed for cytokines and exosomal microRNAs. Data from electronic medical records and clinical outcomes were also correlated. For the animal model, SD rats underwent middle cerebral artery occlusion (MCAO). The mCIMT group received 2 hours of daily intensive limb training for 14 days, starting 7 days post-MCAO, while the control group was untreated. Exosomes were extracted from brain tissue on day 21, followed by nanoparticle tracking and microRNA sequencing. Exosomes from both groups, as well as a vehicle, were injected into the lateral ventricles of MCAO rats, and they were named the Exo-mCIMT group, Exo-control group and vehicle group. Behavioral tests and histopathological staining were performed on day 21 among the three groups. RESULTS: =0.428). In rats, the mCIMT group had a higher concentration of exosomes in brain tissue (3.73e+10 particles/ml) compared to the control group (0.95e+10 particles/ml, P=0.0030). MicroRNA sequencing revealed distinct expression profiles between the groups. Furthermore, the exo-mCIMT group exhibited significantly higher levels of MAP2 and VEGF expression, along with notable improvements in neurobehavioral outcomes. CONCLUSION: These findings suggest that mCIMT promotes neural recovery through increased exosome and microRNA activity in the brain, which plays an important role in neuronal activity after brain injury.