Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure

Abstract

Body-weight supported locomotor training (BWST) promotes recovery of load-bearing stepping in lower mammals, but its efficacy in individuals with a spinal cord injury (SCI) is limited and highly dependent on injury severity. While animal models with complete spinal transections recover stepping with step-training, motor complete SCI individuals do not, despite similarly intensive training. In this review, we examine the significant differences between humans and animal models that may explain this discrepancy in the results obtained with BWST. We also summarize the known effects of SCI and locomotor training on the muscular, motoneuronal, interneuronal, and supraspinal systems in human and non-human models of SCI and address the potential causes for failure to translate to the clinic. The evidence points to a deficiency in neuronal activation as the mechanism of failure, rather than muscular insufficiency. While motoneuronal and interneuronal systems cannot be directly probed in humans, the changes brought upon by step-training in SCI animal models suggest a beneficial re-organization of the systems' responsiveness to descending and afferent feedback that support locomotor recovery. The literature on partial lesions in humans and animal models clearly demonstrate a greater dependency on supraspinal input to the lumbar cord in humans than in non-human mammals for locomotion. Recent results with epidural stimulation that activates the lumbar interneuronal networks and/or increases the overall excitability of the locomotor centers suggest that these centers are much more dependent on the supraspinal tonic drive in humans. Sensory feedback shapes the locomotor output in animal models but does not appear to be sufficient to drive it in humans.

Motor recovery after activity-based training with spinal cord epidural stimulation in a chronic motor complete paraplegic

“…Similar muscle activation patterns were also observed at t7 and t8. While the mechanisms underlying this motor recovery are currently unclear, a recent review by Cote and colleagues 43 supports the view that humans are particularly dependent on residual descending input to generate stepping and standing, and that the human lumbosacral spinal circuitry is more depressed after a severe SCI, compared to other mammals. This assumption is also empirically supported by the fact that tonic, near-motor threshold lumbosacral scES aimed at mimicking the supraspinal tonic drive to the lumbosacral spinal circuitry enabled the generation of motor patterns effective for standing in individuals with chronic, motor complete SCI 17 , 18 .…”

Intensive Functional Neurorehabilitation and Follow-up of 84 Paraplegic Dogs Affected by Intervertebral Disc Disease

“…One of the possible explanations lies in the association between locomotor training and FES that may have facilitated a possible conversion of type II bers to type I (Côté et al, 2017). This is essential for postural support while standing (Postans et al, 2004).…”

“…Furthermore, neuronal plasticity, owing to neurogenesis, gene activation, dendritic modi cations, and changes in physiological properties, as well as glial and vascular plasticity (Wolpaw, 2010) probably to some degree also promote the restoration of motor function secondary to sodium-channel voltage activation (Wolpaw, 2007). This type of step-training increases the e cacy of synaptic connections from residual descending pathways to interneurons located near the lesion (Côté et al, 2017). Therefore, the use of multidisciplinary approaches may improve the functionality (Gomes-Osman et al, 2016; Gant et al, 2018).…”

Understanding exercise-dependent plasticity of motoneurons using intracellular and intramuscular approaches

“…Changes in both passive and active electrophysiological MN properties indicate a reduction in MN excitability in cats (Cope et al 1986;Czéh et al 1978;Hochman and McCrea 1994) and rats (Beaumont et al 2004(Beaumont et al , 2008Button et al 2008;MacDonell et al 2012). On the other hand, there is an increase in spastic contractions that may reflect the activation of PIC (Bennett et al 2001a(Bennett et al , 2001bCôté et al 2017), which would enhance MN excitability or polysynaptic reflexes. While PICs contribute to spasticity development (Brocard et al 2016), other mechanisms have also been shown to contribute to spastic contractions such as decrease in the H-reflex postactivation depression (Lamy et al 2009) and downregulation of the potassium-chloride transporter KCC2 (Boulenguez et al 2010).…”