1. Neuroscience
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Combining robotic training and inactivation of the healthy hemisphere restores pre-stroke motor patterns in mice

Research Article
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Cite this article as: eLife 2017;6:e28662 doi: 10.7554/eLife.28662

Abstract

Focal cortical stroke often leads to persistent motor deficits, prompting the need for more effective interventions. The efficacy of rehabilitation can be increased by 'plasticity-stimulating' treatments that enhance experience-dependent modifications in spared areas. Transcallosal pathways represent a promising therapeutic target, but their role in post-stroke recovery remains controversial. Here, we demonstrate that the contralesional cortex exerts an enhanced interhemispheric inhibition over the perilesional tissue after focal cortical stroke in mouse forelimb motor cortex. Accordingly, we designed a rehabilitation protocol combining intensive, repeatable exercises on a robotic platform with reversible inactivation of the contralesional cortex. This treatment promoted recovery in general motor tests and in manual dexterity with remarkable restoration of pre-lesion movement patterns, evaluated by kinematic analysis. Recovery was accompanied by a reduction of transcallosal inhibition and 'plasticity brakes' over the perilesional tissue. Our data support the use of combinatorial clinical therapies exploiting robotic devices and modulation of interhemispheric connectivity.

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Article and author information

Author details

  1. Cristina Spalletti

    Institute of Neuroscience, CNR, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Claudia Alia

    Institute of Neuroscience, CNR, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Stefano Lai

    The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Alessandro Panarese

    The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Sara Conti

    The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Silvestro Micera

    The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4396-8217
  7. Matteo Caleo

    Institute of Neuroscience, CNR, Pisa, Italy
    For correspondence
    caleo@in.cnr.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4333-6378

Funding

Fondazione Pisa (158/2011)

  • Matteo Caleo

Regione Toscana

  • Silvestro Micera
  • Matteo Caleo

European Union's Horizon 2020 Research and Innovation Program (720270 (HBP SGA1))

  • Silvestro Micera
  • Matteo Caleo

ERC Advanced Grant 2015 (692943)

  • Matteo Caleo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were performed in compliance with the EU Council Directive 2010/63/EU on the protection of animals used for scientific purposes, and approved by the Italian Ministry of Health, protocol number DGSAF0015924-16/06/2015.

Reviewing Editor

  1. Heidi Johansen-Berg, University of Oxford, United Kingdom

Publication history

  1. Received: May 15, 2017
  2. Accepted: December 22, 2017
  3. Accepted Manuscript published: December 27, 2017 (version 1)
  4. Version of Record published: January 10, 2018 (version 2)

Copyright

© 2017, Spalletti et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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