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Review
. 2021 Dec 7:2:755963.
doi: 10.3389/fresc.2021.755963. eCollection 2021.

When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

África Flores  1 , Diego López-Santos  1 , Guillermo García-Alías  1   2
Affiliations
Review

When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

África Flores et al. Front Rehabil Sci. .

Abstract

Electrical neuromodulation has strongly hit the foundations of spinal cord injury and repair. Clinical and experimental studies have demonstrated the ability to neuromodulate and engage spinal cord circuits to recover volitional motor functions lost after the injury. Although the science and technology behind electrical neuromodulation has attracted much of the attention, it cannot be obviated that electrical stimulation must be applied concomitantly to sensorimotor rehabilitation, and one would be very difficult to understand without the other, as both need to be finely tuned to efficiently execute movements. The present review explores the difficulties faced by experimental and clinical neuroscientists when attempting to neuromodulate and rehabilitate manual dexterity in spinal cord injured subjects. From a translational point of view, we will describe the major rehabilitation interventions employed in animal research to promote recovery of forelimb motor function. On the other hand, we will outline some of the state-of-the-art findings when applying electrical neuromodulation to the spinal cord in animal models and human patients, highlighting how evidences from lumbar stimulation are paving the path to cervical neuromodulation.

Keywords: activity-dependent plasticity; neuromodulation; rehabilitation; spinal cord injury; upper limb.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Neurons in the cervical spinal cord. (A) Neural marker (NeuN) immunostaining of a transverse section from a rat C6 spinal segment. The left side shows the spinal section raw immunostaining, depicting the neuronal cell bodies distributed along the dorsal, mid, and ventral gray matter. The right side shows the image analysis performed to categorize and subdivide the identified neurons, based on their soma size and location, in interneurons (light green) and motoneurons (red). (B) The graph shows the mean ± SE of total interneurons and motoneurons quantified from individual serial sections of the cervical spinal cord from three uninjured adult rats. The number of motoneurons follows the anatomy of the cervical enlargement, with increasing numbers at C5–C7, where the motoneuron pools of the forelimb muscles are located (12). In contrast, the number of interneurons is higher at the most rostral cervical segments and gradually decreases along the rostro-caudal axis.
Figure 2
Figure 2
Task specific forelimb motor assessment and rehabilitation. Long-Evans rats are commonly used to study forelimb motor control. In comparison to other rat strains, Long-Evans rats rapidly learn dexterous tasks, which can be associated with a larger cortical motor representation map (41). Different specific motor tasks are being used to assess the animals skills and abilities, including (A) single pellet reaching and grasping, (B) reaching and grasping in a staircase, (C) grip strength, (D) reaching and grasping form a grid, (E) food manipulation, such as pasta or cereals, (F) rope pulling, (G) horizontal ladder, and (H) treadmill locomotion.
Figure 3
Figure 3
Enriched environment rehabilitation. An alternative to task-specific rehabilitation is to engage the animals in an enriched environment in which they have the chance to voluntarily run along rungs, climb the cage walls, nest with the cage sawdust, manipulate food and run in a running wheel.
Figure 4
Figure 4
Spinal cord electrical stimulation. Different approaches have been developed in the last years to neuromodulate the spinal cord. (A) Intraspinal electrodes within the spinal gray matter, close to the motoneuron pools; (B) Epidural electrode arrays are placed over the dorsal side of the spinal cord fixed to the outer side of the meningeal layer; (C) Transcutaneous stimulation is delivered by big size adhesive electrodes which are placed percutaneously on the back skin.
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References

    1. Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, et al. . Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med. (2018) 379:1244–50. 10.1056/NEJMoa1803588 - DOI - PubMed
    1. Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, et al. . Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. (2018) 24:1677–82. 10.1038/s41591-018-0175-7 - DOI - PubMed
    1. Wagner FB, Mignardot J-BB, le Goff-Mignardot CG, Demesmaeker R, Komi S, et al. . Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. (2018) 563:65–93. 10.1038/s41586-018-0649-2 - DOI - PubMed
    1. Morse LR, Field-Fote EC, Contreras-Vidal J, Noble-Haeusslein LJ, Rodreick M, Shields RK, et al. . Meeting proceedings for SCI 2020: launching a decade of disruption in spinal cord injury research. J Neurotrauma. (2021) 38:1251–66. 10.1089/neu.2020.7174 - DOI - PubMed
    1. Grillner S, el Manira A. Current principles of motor control, with special reference to vertebrate locomotion. Physiol Rev. (2019) 100:271–320. 10.1152/physrev.00015.2019 - DOI - PubMed

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