Studies evaluating the pathophysiology of spinal cord ischemia–reperfusion injury (SCIRI) have produced targeted insights across multiple pathways. However, their clinical translation and therapeutic applicability remain limited. This review synthesizes the recent advances in the understanding of SCIRI mechanisms and evaluates emerging therapeutic strategies, providing insights for future research and clinical translation. Using “spinal cord ischemia–reperfusion injury” as the search term, we searched the relevant literature published in the China National Knowledge Infrastructure (CNKI) and PubMed databases. We included 74 articles in the review and analysis. sSCIRI pathogenesis is a self-sustaining vicious cycle, progressing through acute, subacute, and chronic phases. Acutely, ischemia-induced mitochondrial dysfunction triggers excitatory amino acid release and calcium overload, which acts as a critical hub for downstream damage. Subacutely, these events initiate robust neuroinflammation and disrupt the blood–spinal cord barrier, facilitating inflammatory cell infiltration and exacerbating oxidative stress. Chronically, this interplay culminates in widespread neuronal programmed cell death and regeneration-inhibitory glial scar formation, leading to poor neurological outcomes. Current treatments (e.g., glucocorticoids, hyperbaric oxygen) primarily target inflammation and oxidative stress, but they offer limited regenerative benefits. Strategies such as stem cell/exosome therapy, bioactive nanomaterials, and neuromodulation show preclinical potential in promoting axonal regeneration and modulating inhibitory microenvironments, yet clinical translation is hindered by scalability, safety, and delivery standardization. Future efforts must prioritize the development of standardized animal models, combinatorial neuroregenerative approaches, and rigorous translational studies to bridge the gap between experimental findings and clinical efficacy in SCIRI treatment.
Gu et al. (Sun,) studied this question.