Comparative insights into miRNA-mediated repair across nervous system injuries: Implications for histology and...

Neural regeneration in the adult mammalian central nervous system (CNS) is severely restricted by both intrinsic neuronal limitations and an inhibitory post-injury microenvironment. In contrast, the peripheral nervous system (PNS) retains a greater capacity for spontaneous repair. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as key epigenetic regulators of neural regeneration by coordinately modulating multiple genes and signaling pathways involved in axonal growth, neuroinflammation, glial responses, and tissue remodeling. This review summarizes current advances in miRNA-mediated neural repair across both the CNS and PNS, with particular emphasis on their dual roles in regulating intrinsic neuronal growth programs and the extrinsic injury microenvironment. We compare distinct miRNA expression patterns and regenerative mechanisms following neural injury in mammalian and regenerative model systems, highlighting their contributions to axonal regeneration, immune modulation, angiogenesis, and Schwann cell-mediated repair. We further discuss emerging delivery strategies, including exosome-based systems, functionalized nanomaterials, and scaffold-assisted platforms, which improve miRNA stability, targeting efficiency, and therapeutic efficacy. Finally, we examine the major challenges limiting clinical translation, including RNA instability, blood-brain barrier penetration, delivery specificity, and potential off-target effects. Collectively, current evidence suggests that miRNA-based interventions represent a promising therapeutic avenue for neural regeneration and provide new opportunities for developing precision regenerative strategies for nervous system injuries.