MicroRNAs in Spinal Cord Injury: Molecular and Translational Insights

Spinal cord injury (SCI) is characterized by complex molecular and cellular disturbances that contribute to progressive tissue damage and neurological dysfunction. Among the regulatory mechanisms implicated, microRNAs (miRNAs), which are small noncoding RNAs that regulate gene expression posttranscriptionally, have emerged as central components of several injury-related pathways. This review synthesizes current knowledge regarding the regulatory functions of miRNAs and evaluates their potential as therapeutic targets.

Recent experimental and preclinical studies were analyzed to identify key miRNAs associated with injury-induced molecular responses and to assess advances in miRNA-based therapeutic strategies, including the use of miRNA mimics, inhibitors, and delivery systems.

Several miRNAs, including miR-21, miR-223, miR-124, and miR-219, can regulate essential biological processes such as apoptosis, neuroinflammation, oxidative stress, glial activation, and remyelination. miR-21 and miR-223 exhibited context-dependent roles in neuroinflammation, apoptosis, and vascular repair, while miR-124 could modulate microglial activity and miR-219 facilitates oligodendrocyte differentiation and myelin restoration. Experimental therapeutic approaches employing viral vectors, nanoparticles, stem cell-based delivery, and exosome systems have resulted in enhanced tissue preservation, angiogenesis, and functional outcomes in preclinical models.

miRNAs serve as critical molecular regulators and represent promising therapeutic targets. Nevertheless, clinical translation is constrained by challenges such as delivery barriers, off-target effects, and the complexity of miRNA-mediated regulatory networks. Advances in delivery technologies and research focused on precise miRNA regulation may support the development of effective neuroprotective and regenerative therapies.