Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats

  1. Anitha Manohar
  2. Guglielmo Foffani
  3. Patrick D Ganzer
  4. John R Bethea
  5. Karen Moxon  Is a corresponding author
  1. Drexel University, United States
  2. CINAC, Hospital Universitario HM Puerta del Sur, Universidad CEU-San Pablo, Spain

Abstract

After paralyzing spinal cord injury the adult nervous system has little ability to 'heal' spinal connections, and it is assumed to be unable to develop extra-spinal recovery strategies to bypass the lesion. We challenge this assumption, showing that completely spinalized adult rats can recover unassisted hindlimb weight support and locomotion without explicit spinal transmission of motor commands through the lesion. This is achieved with combinations of pharmacological and physical therapies that maximize cortical reorganization, inducing an expansion of trunk motor cortex and forepaw sensory cortex into the deafferented hindlimb cortex, associated with sprouting of corticospinal axons. Lesioning the reorganized cortex reverses the recovery. Adult rats can thus develop a novel cortical sensorimotor circuit that bypasses the lesion, probably through biomechanical coupling, to partly recover unassisted hindlimb locomotion after complete spinal cord injury.

Article and author information

Author details

  1. Anitha Manohar

    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3011-2623
  2. Guglielmo Foffani

    CINAC, Hospital Universitario HM Puerta del Sur, Universidad CEU-San Pablo, Móstoles, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick D Ganzer

    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. John R Bethea

    Department of Biology, Drexel University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Karen Moxon

    School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, United States
    For correspondence
    moxon@ucdavis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5790-097X

Funding

National Science Foundation (CBET 1402984)

  • Anitha Manohar
  • Guglielmo Foffani
  • Patrick D Ganzer
  • John R Bethea

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 animal procedures were conducted in accordance with Drexel University Institutional Animal Care and Use Committee-approved protocols (Protocol# 20069 and Protocol#18374)

Reviewing Editor

  1. Ole Kiehn, Karolinska Institutet, Sweden

Publication history

  1. Received: December 3, 2016
  2. Accepted: June 22, 2017
  3. Accepted Manuscript published: June 29, 2017 (version 1)
  4. Version of Record published: July 6, 2017 (version 2)

Copyright

© 2017, Manohar 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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  1. Anitha Manohar
  2. Guglielmo Foffani
  3. Patrick D Ganzer
  4. John R Bethea
  5. Karen Moxon
(2017)
Cortex-dependent recovery of unassisted hindlimb locomotion after complete spinal cord injury in adult rats
eLife 6:e23532.
https://doi.org/10.7554/eLife.23532
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