Modified constraint-induced movement therapy combined with intermittent theta-burst stimulation promotes functional...

The interaction of modified constraint-induced movement therapy (mCIMT) and intermittent theta-burst stimulation (iTBS) in enhancing stroke recovery is not well understood. This study investigated the effects of mCIMT combined with iTBS therapy on behavioral-functional recovery in stroke rats, with a particular focus on the role of hippocampal synaptic plasticity. We evaluated the behavioral functions of rats post-stroke using the fault footsteps test, modified neurology severity score (mNSS), elevated plus maze (EPM), and Y-maze tests, subsequently employing Golgi staining and transmission electron microscopy to further examine synaptic plasticity in the hippocampal region. In addition, the Pearson correlation coefficient was employed to analyze how synaptic plasticity-related metrics (the dimension of postsynaptic density and the proportion of mature dendritic spines) relate to motor metrics (the fault footsteps ratio) and emotional metrics (EPM: the proportion of open-arm entries and the proportion of time in open arms). Our research indicated that mCIMT combined with iTBS therapy may differentially affect the hippocampal CA1 and CA3 regions. This combined therapy may primarily enhance motor performance and alleviate anxiety-like behavior in stroke rats by promoting synaptic plasticity in the ipsilateral hippocampal CA1 region while exerting a limited impact on spatial memory. The present study provides evidence at the structural and functional levels for the potential mechanisms of mCIMT combined with iTBS therapy in stroke rehabilitation. The significance of synaptic plasticity in the CA1 region regarding therapy efficacy may be further investigated in the future.