Regeneration and remyelination promoting effects of spinal cord stimulation following spinal cord injury: A scoping review

Abstract

Introduction: Spinal cord injury (SCI) disrupts crucial neural pathways and causes severe neurological deficits that impact the quality of life. Although preliminary research has shown some promise of Spinal Cord Stimulation (SCS) in promoting axonal regeneration and remyelination, a clear understanding of the pertinent literature remains lacking. This scoping review consolidates evidence on the effects of SCS in promoting axonal growth and myelin development, preserving spared tissue integrity, and facilitating functional recovery following SCI. Methods: Pre-clinical studies from 1946 to 2024 that involved the application of SCS in experimental SCI models, and compared outcomes with no-stimulation controls were included. Data extraction focused on injury characteristics, stimulation protocols, markers of axonal regeneration, remyelination, and functional recovery. Results: Twenty-one studies met the inclusion criteria. Twelve reported elevated pro-regenerative markers and reduced inhibitory/apoptotic factors in SCS-treated cohorts. Ten demonstrated enhanced axonal preservation, increased axonal length, or a greater number of axons. Nine showed increased myelin content, myelin thickness, and oligodendrocyte differentiation. Twenty studies assessed locomotor outcomes through behavioral and electrophysiological tests, consistently demonstrating SCS-mediated functional recovery. Discussion: Overall, SCS led to improved remyelination, axonal regeneration, and locomotor/electrophysiological function in rodent SCI models. Although the published literature supports the therapeutic potential of SCS for functional recovery, future research should refine stimulation parameters, delivery methods and timing of intervention. Specific issues of translational importance that were found lacking include autonomic recovery (2 of 21 reported), standardized outcomes, reporting common elements, and combination therapies.