Current treatments for SCIs

The contemporary era of neurosurgery has revolutionized SCI treatment through the introduction of precise surgical techniques. Decompression and stabilization are established components of human SCI management when clinically indicated, particularly for relieving compression and restoring spinal stability. Animal studies have further helped clarify timing, mechanisms, and biological effects of decompression after SCI [21]. A limited human case series has reported functional improvements after peripheral nerve grafting combined with a biomaterial scaffold, but these findings should be interpreted cautiously because they are not yet supported by large controlled clinical trials [22, 23].

Similar technological leaps further amplify surgical advancements. In animal models, EES and DBS have provided mechanistic evidence that neuromodulation can influence spinal and supraspinal motor circuits after SCI. However, these findings should be distinguished from human clinical studies of EES, which have demonstrated selected functional gains in small cohorts of individuals with SCI [24–26]. Additionally, regenerative therapies, including neural progenitor cell-based approaches, have shown potential in preclinical and early translational studies, but their clinical efficacy, durability, and generalizability remain uncertain [27].

EES directs a current of electricity to the dorsal aspect of the spinal cord through surgically implanted electrodes [28]. Depending on the stimulation parameters, particularly frequency, there are differential patterns of movement. EES works by depolarizing large diameter afferents, which in turn activate lumbar interneurons that are involved in lower limb motor control. Mechanistic and computational studies suggest that EES activates large-diameter afferents and spinal interneuronal networks involved in lower-limb motor control. In selected human studies, EES combined with intensive rehabilitation has enabled some participants with SCI to stand, support weight, or take assisted steps [29, 30].

Transcranial magnetic stimulation (TMS), particularly high-frequency repetitive TMS (HF-rTMS), has emerged as a noninvasive approach with potential to modulate corticospinal excitability and promote activity-dependent plasticity. In experimental models, activation of MAP2K signaling through genetic engineering or HF-rTMS promoted corticospinal axon sprouting and functional regeneration, suggesting a potential translational pathway for enhancing endogenous repair mechanisms after SCI. However, these findings remain primarily experimental and require further validation in human SCI populations [31].

Robotic therapy for SCIs relies on a device that stimulates repetitive proprioceptive input from the limbs [32]. This input may promote neuroplasticity, defined here as activity-dependent reorganization and strengthening of spared neural pathways through repeated sensory feedback, motor practice, and reinforcement of residual spinal and supraspinal circuits. These activity-dependent interventions aim to strengthen residual motor pathways and improve functional limb movement. In human rehabilitation studies and meta-analyses, robot-assisted gait training has been associated with improvements in walking ability and lower-limb strength in some individuals with SCI, although outcomes vary by injury completeness, baseline function, and training intensity [33].

There are a number of pharmacological interventions designed to address SCIs. Some examples include minocycline, fampridine, and hepatocyte growth factor (HGF) [34, 35]. Minocycline targets multiple processes that are involved in mediating cell death and prevents the progression of secondary injury following a spinal cord injury [34]. Some pharmacologic agents have been evaluated in human or clinical contexts, including minocycline and fampridine, although efficacy remains variable and not universally established. Other agents, such as HGF, have shown regenerative potential in experimental and early translational settings, but they should not be presented as established clinical therapies for SCI [35].

Cell-based approaches, such as human embryonic stem cells, adult stem cells, and fetal-derived neural cells remain an important area of SCI research, particularly for axonal regeneration, remyelination, and modulation of the post-injury microenvironment [36–38]. Similarly, biomaterial scaffolds and hydrogels may support SCI repair by bridging lesion cavities, modulating scar formation, or delivering cells, growth factors, or drugs [39].

NMES is used to increase the strength of partially paralyzed muscles in people who are affected by SCIs [40]. Combining NMES with FES has been shown to induce hypertrophy in weakened muscles [40]. tSCS is a noninvasive neuromodulatory technique that delivers electrical stimulation to spinal sensorimotor circuits through surface electrodes placed over the skin, typically overlying the targeted spinal segments. When combined with intensive rehabilitation, tSCS may enhance motor function by promoting activity-dependent neuroplasticity [41]. Combining this procedure with intense exercise aims to restore movement and function through neuroplasticity [42].

Together, these treatment strategies demonstrate the multifaceted progress being made in SCI management while also highlighting the ongoing need for approaches that can more directly integrate neural signal decoding, targeted stimulation, and activity-dependent rehabilitation, as seen in emerging closed-loop neuromodulation and BSI technologies.