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

Abstract

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 periinfarct 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.

Experimental and Computational Study on Motor Control and Recovery After Stroke: Toward a Constructive Loop Between Experimental and Virtual Embodied Neuroscience

“…Possible problems could arise from the alignment of the experimental data, especially after the stroke, due to the shrinkage and the movement of the tissue (Brown et al, 2007 ; Allegra Mascaro et al, 2019 ). We have tried to avoid this by excluding from the analysis the regions adjacent to the stroke, but this reduces the predictive value of the model due to smaller number of analyzed regions.…”

“…In addition, higher resolution SC performed with light-sheet microscopy on individual mice (Allegra Mascaro et al, 2015 ) could test the model prediction at the final time point of the experiment. As a final step, an individualized therapy could be proposed targeting specific parts of the brain (Spalletti et al, 2017 ; Allegra Mascaro et al, 2019 ; Conti et al, 2020 ), depending on the location and the size of the stroke.…”

“…We propose a framework (“ Embodied brain closed loop ”) endowed with a library of modeling tools that will eventually allow to realize entirely virtual experiments. We focused on an experiment on motor control and motor recovery after stroke described in Spalletti et al ( 2017 ) and Allegra Mascaro et al ( 2019 ), whose simulation requires two main tiles. The first is the realization of voluntary movements in a virtual milieu.…”

Experimental and computational study on motor control and recovery after stroke: towards a constructive loop between experimental and virtual embodied neuroscience

“…In addition, higher resolution SC performed with light-sheet microscopy on individual mice (Allegra Mascaro et al, 2015) could test the model prediction at the final time point of the experiment. As a final step, an individualized therapy could be proposed targeting specific parts of the brain (Spalletti et al (2017), Allegra Mascaro et al (2019) and Conti et al (2020)), depending on the location and the size of the stroke.…”

“…We propose a framework (“ Embodied brain closed loop ”) endowed with a library of modeling tools that will eventually allow to realize entirely virtual experiments. We focused on an experiment on motor control and motor recovery after stroke described in Spalletti et al (2017) and Allegra Mascaro et al (2019), whose simulation requires two main tiles. The first is the realization of voluntary movements in a virtual milieu.…”