Figure 1. Schematic diagram of a spinal cord contusion injury describing white matter (highlighted in red) injury. Some of the events of spinal cord injury that contribute to white matter damage (A–G) are: (A) loss of myelin (primary demyelination), which impedes normal axonal function; (B) disruption of axons which results in degeneration and retraction of the axonal stump, both proximal and distal to the injury site; (C) an increase in ‘inhibitory’ molecules following injury (e.g. associated with myelin degradation or ‘glial scarring’) that prevent axonal growth (sprouting/regeneration); (D) activation of glial cells, which contributes to formation of a glial scar around the injury site that acts as a physical and molecular barrier to axonal growth and (E) disruption of blood vessels that supply the spinal cord. This disruption not only impedes delivery of oxygen (i.e. causes ischaemia) but also results in bleeding (F – red blood cells and G – white blood cells) into the spinal cord tissue, contributing to secondary tissue damage. Treatment approaches to improve white matter repair include (i) limiting the effect of demyelination and promotion of ‘remyelination’ by delivery of myelin precursor cells; (ii) cell transplantation as a means of ‘bridging’ the injury site and providing a substrate that is more permissive to axonal growth and/or regeneration; (iii) delivery of growth-promoting factors (trophic factors) into the injured spinal cord to enhance the axonal ability for growth; (iv) attenuation of the inhibitory affects of some injury-related molecules (e.g. delivery of drugs that block inhibitory myelin-associated molecules provide an environment that is more permissive to axonal growth/regeneration) and (v) delivery of anti-inflammatory agents to regulate the immune response following spinal injury and limit any potentially harmful affects.

Figure 2. Schematic diagram of a spinal contusion injury demonstrating cell transplantation as a treatment for grey matter (neuronal) damage. In addition to axonal damage there is extensive neuronal (motoneuron and interneuron) loss as a result of trauma and subsequent degenerative processes (a). Transplantation of immature cells capable of becoming neurons offers potential for replacing those neurons lost after injury (b). The newly transplanted cells may form connections with neurons of the injured spinal cord (around or below the injury site), thereby forming what would represent a novel relay circuit (c).

Figure 3. Descending supraspinal (originating from the brainstem or brain) axons innervate interneurons and motoneurons on both sides of the spinal cord (a). Spinal cord injury results in disruption of these descending axons (demonstrated by a partial lesion in (b)). Following partial spinal cord injury, new, alternative pathways can spontaneously develop over time. This form of neuroplasticity can arise due to new growth or ‘sprouting’ of injured axons (c) onto interneurons that in turn form connections with neurons below the lesion, thereby forming an alternative pathway. Similarly, uninjured axons (spared by the injury) can undergo ‘sprouting’ to form alternative pathways (d). Such alternative pathways may serve to compensate for the original circuit lost due to injury.

Figure 4. Images showing the progression of locomotor training in an individual with incomplete spinal cord injury: (a) Retraining stepping and balance on the treadmill – partial body support environment with trainers manually assisting limb/trunk movements. (b) Translation of skills learned in the treadmill environment to assisted walking over ground. (c) Translation of locomotor skills developed to self-assisted walking within the community.