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

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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.

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Funding

This work was supported by research funding from the Department of Neurosurgery, University of New Mexico (UNM) Hospital, Albuquerque, NM, USA.

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  1. Department of Neurosurgery, University of New Mexico (UNM) School of Medicine, Albuquerque, NM, 87131, USA

    Syed Faraz Kazim, Christian A. Bowers, Chad D. Cole & Meic H. Schmidt

  2. School of Medicine, University of New Mexico (UNM), Albuquerque, NM, 87131, USA

    Samantha Varela

  3. School of Medicine, New York Medical College (NYMC), Valhalla, NY, 10595, USA

    Zafar Karimov, Erick Martinez & Jonathan V. Ogulnick

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SFK, CAB, CDC, and MHS wrote the initial draft and edited the final version of the manuscript. SV, ZK, JO, and EM contributed to the manuscript editing. MHS provided overall supervision for the manuscript.

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Kazim, S.F., Bowers, C.A., Cole, C.D. et al. Corticospinal Motor Circuit Plasticity After Spinal Cord Injury: Harnessing Neuroplasticity to Improve Functional Outcomes. Mol Neurobiol 58, 5494–5516 (2021). https://doi.org/10.1007/s12035-021-02484-w

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