Electrical Stimulation as a Tool to Promote Plasticity of the Injured Spinal Cord

Abstract

Unlike their peripheral nervous system counterparts, the capacity of central nervous system neurons and axons for regeneration after injury is minimal. Although a myriad of therapies (and different combinations thereof) to help promote repair and recovery after spinal cord injury (SCI) have been trialed, few have progressed from bench-top to bedside. One of the few such therapies that has been successfully translated from basic science to clinical applications is electrical stimulation (ES). Although the use and study of ES in peripheral nerve growth dates back nearly a century, only recently has it started to be used in a clinical setting. Since those initial experiments and seminal publications, the application of ES to restore function and promote healing have greatly expanded. In this review, we discuss the progression and use of ES over time as it pertains to promoting axonal outgrowth and functional recovery post-SCI. In doing so, we consider four major uses for the study of ES based on the proposed or documented underlying mechanism: (1) using ES to introduce an electric field at the site of injury to promote axonal outgrowth and plasticity; (2) using spinal cord ES to activate or to increase the excitability of neuronal networks below the injury; (3) using motor cortex ES to promote corticospinal tract axonal outgrowth and plasticity; and (4) leveraging the timing of paired stimuli to produce plasticity. Finally, the use of ES in its current state in the context of human SCI studies is discussed, in addition to ongoing research and current knowledge gaps, to highlight the direction of future studies for this therapeutic modality.

Keywords: SCI; axonal outgrowth; axonal regeneration; neuromodulation; neuroplasticity plasticity; treatment.

FIG. 1.

The difference in the approach and location of electrical stimulation following spinal cord injury of the four applications discussed in this review are summarized. (A) Cortical stimulation to activate growth promoting cellular pathways with the intention to promote axonal outgrowth (i.e., collateral sprouting and regeneration). (B) Using electrical fields across the spinal lesion to promote axonal growth (i.e., regeneration) through the lesion. (C) Paired stimulation (here cortex and a peripheral nerve) to strengthen synaptic connections by coactivating pre- and post-synaptic neurons. (D) Electrical stimulation to activate (or facilitate activation) of spinal circuitry below the level of the injury.