In this review we will describe newly developed techniques that are being used to recover levels of motor function after a severe spinal cord injury that have not been observed previously. These new approaches include pharmacological neuromodulation and/or epidural stimulation of the spinal cord circuitries in combination with motor training. By combining the increased levels of excitability of the interneuronal spinal circuitries using these interventions and the ability of the spinal circuitries to interpret and respond appropriately to ongoing complex ensembles of sensory input, the peripheral sensory system can become an effective source for the control of motor function. Similar types of neuromodulation have been shown to enable the brain to regain functional connectivity with the spinal cord circuitries below a clinically complete spinal cord lesion. In fact, some level of voluntary control of movement has been observed in subjects with complete paralysis in the presence of epidural stimulation. The biological mechanisms thought to underlie the recovery of motor function after a severe spinal cord injury are based on decades of research on a wide range of animal models. Fortunately the extensive conservation of neural mechanisms of motor control has provided a window for gaining considerable insight into the mechanisms of recovery of motor function in humans.
"First established in spinalized cats , , the effectiveness of TMT has been demonstrated in rodent models with variable injury severities and training regimens . A recent study showed that epidural stimulation can effectively reactivate the lumbar motor circuitry to become more sensitive to sensory inputs provided by treadmill training (TMT) , raising a hope that TMT in combination with electrical stimulation and/or pharmacological neuromodulation  could be an effective therapeutic option to improve locomotor function after SCI . "
[Show abstract][Hide abstract] ABSTRACT: Traumatic spinal cord injury (SCI) often leads to debilitating loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9. Another group of rats received treadmill locomotor training (TMT) until 3 weeks, and gene expression profiles were compared between animals with and without TMT. Microarray analysis showed that many inflammation-related genes were robustly upregulated in the lumbar spinal cord at both 1 and 3 weeks after thoracic injury. Notably, several components involved in an early complement activation pathway were concurrently upregulated. In line with the microarray finding, the number of microglia substantially increased not only in the white matter but also in the gray matter. C3 and complement receptor 3 were intensely expressed in the ventral horn after injury. Furthermore, synaptic puncta near ventral motor neurons were frequently colocalized with microglia after injury, implicating complement activation and microglial cells in synaptic remodeling in the lumbar locomotor circuitry after SCI. Interestingly, TMT did not influence the injury-induced upregulation of inflammation-related genes. Instead, TMT restored pre-injury expression patterns of several genes that were downregulated by injury. Notably, TMT increased the expression of genes involved in neuroplasticity (Arc, Nrcam) and angiogenesis (Adam8, Tie1), suggesting that TMT may improve locomotor function in part by promoting neurovascular remodeling in the lumbar motor circuitry.
PLoS ONE 02/2014; 9(2):e88215. DOI:10.1371/journal.pone.0088215 · 3.23 Impact Factor
"Patients can be trained to step with body weight support unassisted, but they use activity patterns in individual muscles that were often different from healthy individuals. A number of clinical trials have suggested the possible beneficial effects of locomotor training in SCI patients (Edgerton and Roy, 2012). In patients with severe SCI disorders, initial training is performed while being supported by a harness or with their body partially unloaded. "
[Show abstract][Hide abstract] ABSTRACT: Human locomotor movements exhibit considerable variability and are highly complex in terms of both neural activation and biomechanical output. The building blocks with which the central nervous system constructs these motor patterns can be preserved in patients with various sensory-motor disorders. In particular, several studies highlighted a modular burst-like organization of the muscle activity. Here we review and discuss this issue with a particular emphasis on the various examples of adaptation of locomotor patterns in patients (with large fiber neuropathy, amputees, stroke and spinal cord injury). The results highlight plasticity and different solutions to reorganize muscle patterns in both peripheral and central nervous system lesions. The findings are discussed in a general context of compensatory gait mechanisms, spatiotemporal architecture and modularity of the locomotor program.
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