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      A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

      review-article
      1 , 2 , 3 , *
      Neural Plasticity
      Hindawi Publishing Corporation

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          Abstract

          Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI.

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          Most cited references199

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          The H-reflex as a probe: pathways and pitfalls.

          The Hoffmann (or H) reflex is considered a major probe for non-invasive study of sensorimotor integration and plasticity of the central nervous system in humans. The first section of this paper reviews the neurophysiological properties of the H-reflex, which if ignored create serious pitfalls in human experimental studies. The second section reviews the spinal inhibitory circuits and neuronal pathways that can be indirectly assessed in humans using the H-reflex. The most confounding factor is that reciprocal, presynaptic, and Ib inhibition do not act in isolation during movement. Therefore, characterization of these spinal circuits should be more comprehensive, especially in cases of a neurological injury because neurophysiological findings are critical for the development of successful rehabilitation protocols. To conclude, the H-reflex is a highly sensitive reflex with an amplitude that is the result of complex neural mechanisms that act synchronously. If these limitations are recognized and addressed, the H-reflex constitutes one of the major probes to assess excitability of interneuronal circuits at rest and during movement in humans.
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            Extensive Spontaneous Plasticity of Corticospinal Projections After Primate Spinal Cord Injury

            While axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, adult rhesus monkeys underwent C7 spinal cord hemisections, with subsequent analysis of behavioral, electrophysiological and anatomical adaptations. We found remarkable spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.
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              Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors.

              Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy.
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                Author and article information

                Journal
                Neural Plast
                Neural Plast
                NP
                Neural Plasticity
                Hindawi Publishing Corporation
                2090-5904
                1687-5443
                2016
                11 May 2016
                : 2016
                : 1216258
                Affiliations
                1Interdepartmental Neuroscience Program, Northwestern University, Chicago, IL 60611, USA
                2The Graduate Center, City University of New York, New York, NY 10016, USA
                3Department of Physical Therapy, College of Staten Island, City University of New York, Staten Island, NY 10314, USA
                Author notes

                Academic Editor: Alain Frigon

                Author information
                http://orcid.org/0000-0001-5020-8094
                http://orcid.org/0000-0002-6277-236X
                Article
                10.1155/2016/1216258
                4879237
                27293901
                4ef47928-409d-4ef5-9a81-dc341c2c58a1
                Copyright © 2016 A. C. Smith and M. Knikou.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 December 2015
                : 20 April 2016
                Categories
                Review Article

                Neurosciences
                Neurosciences

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