Abstract
Spinal cord injury (SCI) remains one of the most devastating neurological conditions with poor prognosis and limited therapeutic options. Early surgical decompression has been established as the cornerstone of acute management, yet multiple pharmacologic strategies have been extensively investigated to improve neurological outcomes. High-dose methylprednisolone sodium succinate, once widely adopted, ultimately failed to demonstrate consistent efficacy, underscoring the challenges of translating preclinical promise into clinical benefit. Advances in understanding the sequential pathophysiology of SCI, including excitotoxicity, oxidative stress, inflammation, apoptosis, glial scarring, and chronic inhibitory signaling, have broadened therapeutic targets across temporal phases of injury. In this narrative review, we revisit historical pharmacologic therapies such as corticosteroids, and highlight current and emerging candidates including riluzole, minocycline, granulocyte colony-stimulating factor, and biologics targeting the Rho/ROCK pathway (Cethrin, anti-Nogo-A, and anti-repulsive guidance molecule A antibodies). Although compelling preclinical evidence exists, most clinical trials have been limited by patient heterogeneity, narrow therapeutic time windows, and outcome assessment challenges, preventing any drug from achieving guideline-level endorsement. Future success will likely depend on tailored multimodal regimens according to patient stratification, optimized therapeutic timing and delivery, and integration with surgical decompression, hemodynamic management, rehabilitative interventions, and novel bioengineered strategies. Continued efforts in these directions remain essential to establish pharmacologic therapy as a critical component of multimodal SCI care.