Neuroplasticity of spinal cord injury and repair

The sudden loss of movement after spinal cord injury (SCI) is life-changing and is a major impetus to study spinal cord motor system plasticity and devise novel repair strategies. This review focuses on the motor cortex and the corticospinal tract, which are key to producing voluntary movements. The motor cortex projects directly to the spinal cord, via the corticospinal tract, and indirectly, via relays in the brain stem. With loss of the corticospinal tract after SCI, the indirect paths may bypass the injury and play an important role in voluntary control. In health and after injury, the spinal cord is a key site for activity-dependent neuroplasticity of the corticospinal system. Three kinds of activity-dependent plasticity have been identified: (1) corticospinal tract axon sprouting after electrical stimulation of the motor cortex; (2) synaptic competition between corticospinal tract and proprioceptive afferent fiber terminations; and (3) long-term potentiation (LTP) at the corticospinal tract-spinal interneuron synapse. SCI damages descending motor pathway connections and, in turn, triggers a loss of down-stream activity-dependent processes. This activity loss produces spinal interneuron degeneration and several activity-dependent maladaptive changes that underly hyperreflexia, spasticity, and spasms. Animal studies show that phasic electrical and tonic direct current stimulation can be used to supplement activity after SCI to reduce the activity-dependent degenerative and maladaptive changes. Importantly, when applied chronically neuromodulation recruits spinal neuroplasticity to improve function after SCI by promoting activity-dependent corticospinal axon sprouting and synapse formation. This helps establish new functional connections and strengthens spared connections. Combining neuromodulation to promote repair and motor rehabilitation to train circuits can most effectively promote motor recovery.