Challenges and opportunities for repairing the injured spinal cord: inflammation, regeneration, and functional reconstruction

Spinal cord injury is a leading cause of disability worldwide, with profound physical, psychological, and socioeconomic impacts. Despite advances in medical care, there remains an urgent need for effective treatments that minimize side effects while promoting recovery. Prompt intervention following spinal cord injury is crucial, as it has the potential to mitigate secondary damage and improve outcomes. Among the secondary responses to spinal cord injury, neuroinflammation plays a central role in driving the pathological progression of both the acute and chronic phases of injury. This complex physiological response, triggered by mechanical, chemical, or immunological insults, involves a cascade of cellular and molecular events that can either exacerbate tissue damage or support repair and recovery, depending on its regulation. In this review, we provide a comprehensive overview of the primary inflammatory mechanisms that arise following spinal cord injury, detailing the key cellular players and molecular mediators involved. We also examine the dual nature of neuroinflammation, highlighting its detrimental and reparative roles in the context of spinal cord injury pathology. Furthermore, we explore emerging therapeutic strategies aimed at modulating inflammation to enhance functional recovery. Particular focus has been placed on recent preclinical studies using animal models to evaluate novel anti-inflammatory treatments and therapeutic agents. These findings underscore the potential of targeting inflammation as a promising avenue for promoting spinal cord injury repair, paving the way for finding effective therapeutic strategies to promote nerve regeneration and functional recovery.