Neuroplasticity in Spinal Cord Injury: A Scoping Review of Characterized Mechanisms

Background/Objectives: Neuroplasticity is crucial for functional adaptation after spinal cord injury (SCI). Both adaptive/maladaptive changes occur across the cortical/subcortical/spinal levels, influencing recovery, compensation, and long-term complications. However, the contributions of these mechanisms remain unclear. This study investigated the current evidence on neuroplastic mechanisms following SCI, identifying knowledge gaps relevant to rehabilitation/functional recovery. Methods: This scoping review searched the PubMed, Scopus, and Cochrane databases from inception to 14 November 2025. Neuroimaging/electrophysiological methods used to investigate neuroplastic changes in human SCI were assessed. Data on study design, participant characteristics, injury features, methodological approaches, and reported neuroplastic mechanisms were extracted. Findings were categorized into predefined domains (axonal regeneration, synaptic plasticity, cortical reorganization, propriospinal pathway reorganization, neurochemical and molecular changes, activity-dependent plasticity, maladaptive plasticity and other mechanisms). Results: Across 37 studies, cortical reorganization was most commonly reported (n = 19), followed by activity-dependent plasticity (n = 14), and synaptic plasticity (n = 12). Propriospinal pathway reorganization and maladaptive plasticity were reported in six and four studies, respectively. Evidence on axonal regeneration (n = 1) and neurochemical/molecular mechanisms (n = 2) were limited. Neuroimaging/electrophysiological findings demonstrated dynamic cortical reorganization, altered sensorimotor network connectivity, and progressive structural changes in motor pathways. Activity-dependent interventions, including task-specific training, motor imagery, and neuromodulation, would appear to promote adaptive plasticity, while maladaptive changes are associated with neuropathic pain, abnormal excitability, and compensatory overactivation. Conclusions: Neuroplasticity after SCI involves multiple interactions with cortical/spinal mechanisms. Cortical reorganization and activity-dependent plasticity were the most frequently investigated neuroplasticity domains identified in the included studies, while axonal regeneration and molecular mechanisms remain underexplored in humans. Future multimodal longitudinal studies are needed to clarify these relationships and optimize rehabilitation strategies.