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

Year: 2019

Authors: Allegra Mascaro LM., Conti E., Lai S., Di Giovanna AP., Spalletti C., Alia C., Panarese A., Scaglione A., Sacconi L., Micera S., Caleo M., Pavone FS.

Autors Affiliation: CNR, Neurosci Inst, I-56124 Pisa, Italy; Florence, European Lab Nonlinear Spect, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, I-50019 Sesto Fiorentino, Italy; Scuola Super Sant Anna, BioRobot Inst, Translat Neural Engn Area, I-56127 Pisa, Italy; CNR, Natl Inst Opt, I-50019 Sesto Fiorentino, Italy; Ecole Polytech Fed Lausanne, Ctr Neuroprosthet, Bertarelli Fdn Chair Translat NeuroEngn, CH-1015 Lausanne, Switzerland; Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland; Univ Padua, Dept Biomed Sci, I-35131 Padua, Italy

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 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.

Journal/Review: CELL REPORTS

Volume: 28 (13)      Pages from: 3474-1  to: 3474-18

More Information: We thank Alessio Masi and Marie Caroline Muellenbroich for very useful discussions about the manuscript and Giuseppe De Vito for assistance on statistics analysis. We thank Dr. Zanier from the Mario Negri Institute (Milan) for providing reagents for immunohistochemical analysis. We thank the mechanics and electronics workshops at LENS. We thank K. Deisseroth for opsin plasmids. This project has received funding from the H2020 EXCELLENT SCIENCE – European Research Council (ERC) under grant agreement 692943 BrainBIT. In addition, it was supported by the European Union´s Horizon 2020 Research and Innovation Programme under Grant Agreements 720270 (HBP SGA1), 785907 (HBP SGA2), and 654148 (Laserlab-Europe). Part of this work was performed within the framework of the Proof of Concept Studies for the ESFRI research infrastructure project Euro-BioImaging at the PCS facility LENS.
DOI: 10.1016/j.celrep.2019.08.062

Citations: 35
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