Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes

Mol Neurobiol. 2021 Nov;58(11):5494-5516. doi: 10.1007/s12035-021-02484-w. Epub 2021 Aug 3.

Abstract

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.

Keywords: Corticospinal motor circuit; Neuromodulation; Neuroplasticity; Rehabilitation; Spinal cord injury.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain-Computer Interfaces
  • Combined Modality Therapy
  • Electric Stimulation Therapy
  • Humans
  • Locomotion / physiology
  • Low-Level Light Therapy
  • Motor Cortex / physiopathology
  • Nerve Regeneration
  • Neuronal Outgrowth
  • Neuronal Plasticity*
  • Neuroprotective Agents / therapeutic use
  • Photochemotherapy
  • Pyramidal Tracts / physiopathology*
  • Quality of Life
  • Recovery of Function
  • Riluzole / therapeutic use
  • Spinal Cord / physiopathology
  • Spinal Cord Diseases / rehabilitation
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy
  • Stem Cell Transplantation
  • Transcranial Direct Current Stimulation
  • Transcutaneous Electric Nerve Stimulation

Substances

  • Neuroprotective Agents
  • Riluzole