Emerging Therapeutic Strategies for Traumatic Spinal Cord Injury

Spinal cord injury (SCI) is a debilitating neurologic condition with tremendous socioeconomic impact on affected individuals and the health care system. The treatment of SCI principally includes surgical treatment and marginal pharmacologic and rehabilitation therapies targeting secondary events with minor clinical improvements. This unsuccessful result mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiologic changes that occur in the injured spinal cord. Once the nervous system is injured, cascades of cellular and molecular events are triggered at varying times. Although the cascade of tissue reactions and cell injury develops over a period of days or weeks, the most extensive cell death in SCI occurs within hours of trauma. This situation suggests that early intervention is likely to be the most promising approach to rescue the cord from further and irreversible cell damage. Over the past decades, a wealth of research has been conducted in preclinical and clinical studies with the hope to find new therapeutic strategies. Researchers have identified several targets for the development of potential therapeutic interventions (e.g., neuroprotection, replacement of cells lost, removal of inhibitory molecules, regeneration, and rehabilitation strategies to induce neuroplasticity). Most of these treatments have passed preclinical and initial clinical evaluations but have failed to be strongly conclusive in the clinical setting. This narrative review provides an update of the many therapeutic interventions after SCI, with an emphasis on the underlying pathophysiologic mechanisms.