Constraint-Induced Movement Therapy Modulates Neuron Recruitment and Neurotransmission Homeostasis of the Contralesional Cortex to Enhance Function Recovery after Ischemic Stroke

Abstract

Stroke often results in long-term and severe limb dysfunction for a majority of patients, significantly limiting their activities and social participation. Constraint-induced movement therapy (CIMT) is a rehabilitation approach aimed explicitly at enhancing upper limb motor function following a stroke. However, the precise mechanism remains unknown. This study explores how CIMT may alleviate forelimb paralysis in ischemic mice, potentially through structural and functional remodeling of brain regions beyond the infarct area, especially the contralateral cortex. We demonstrated that CIMT recruits neurons from the contralesional cortex into the network that innervates the affected forelimb, as evidenced by PRV retrograde nerve tracing. Additionally, we investigated how CIMT influences synaptic plasticity in the contralateral cortex by evaluating synaptic growth marker levels and neurotransmission’s homeostatic regulation. Our findings uncover a rehabilitative mechanism by which CIMT treats ischemic stroke, characterized by increased recruitment of neurons from the contralateral cortex into the network that innervates the affected forelimb, facilitated by homeostatic regulation of neurotransmission.