Combined Rehabilitation Promotes the Recovery of Structural and Functional Features of Healthy Neuronal Networks after Stroke

Summary: Rehabilitation is considered the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor improvement prompted by rehabilitative therapy. Previous work showed that robotic training combined with transient inactivation of the contralesional cortex promotes a generalized recovery in a mouse model of stroke. Here, we use advanced optical imaging and manipulation tools to study cortical remodeling induced by this rehabilitation paradigm. We show that the stabilization of peri-infarct synaptic contacts accompanies increased vascular density induced by angiogenesis. Furthermore, temporal and spatial features of cortical activation recover toward pre-stroke conditions through the progressive formation of a new motor representation in the peri-infarct area. In the same animals, we observe reinforcement of inter-hemispheric connectivity. Our results provide evidence that combined rehabilitation promotes the restoration of structural and functional features distinctive of healthy neuronal networks. : Robotic training combined with transient contralesional inactivation was recently shown to promote a generalized recovery after stroke. Here, Allegra Mascaro et al. investigate how this rehabilitation paradigm affects neuronal and vascular plasticity of the mouse cortex. Synaptic stabilization is associated with angiogenesis and recovery of a segregated motor representation. Keywords: robotic rehabilitation, pharmacological therapy, two-photon microscopy, in vivo, cerebral cortex, spine plasticity, photothrombosis, optogenetics, calcium imaging, angiogenesis