Neural Repair and Regeneration After Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that disrupts central nervous system function, leading to significant disability and reduced quality of life. Globally, over 20 million individuals live with SCI, with rising incidence driven by trauma, particularly in developing nations. SCI pathophysiology involves primary mechanical damage followed by complex secondary injury cascades, including ischemia, inflammation, oxidative stress, excitotoxicity, and apoptosis. Chronic stages are marked by glial scar formation and neurocircuitry disruption. Therapeutic strategies target neuroprotection and neuroregeneration. Neuroprotective agents such as methylprednisolone, minocycline, riluzole, and IVIG modulate inflammation, apoptosis, and excitotoxicity, though clinical outcomes remain mixed. Neural regenerative strategies aim to restore function through axonal growth promotion and circuit reactivation. These include monoclonal antibodies against inhibitors like Nogo-A and RGMa, stem cell therapies (neural stem cells, mesenchymal stem cells, oligodendrocyte progenitor cells), and gene therapy using vectors like AAV and CRISPR/Cas9 to enhance growth factor expression or suppress inhibitory pathways. Biomaterials, including hydrogels and scaffolds, support cell survival and integration, while neuromodulation techniques such as epidural spinal cord stimulation (eSCS) enhance circuit plasticity and functional recovery. Despite these advances, challenges remain in optimizing therapeutic efficacy, delivery mechanisms, and integration within the hostile injury microenvironment. Future approaches will likely incorporate combinatorial therapies to synergize neuroprotection, regeneration, and neuromodulation for improved outcomes. This review summarizes the current understanding of SCI pathophysiology, highlights emerging therapeutic strategies, and outlines the trajectory for future research aimed at achieving meaningful functional recovery.