Background: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. Methods: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. Results: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50–26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15–28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25–35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. Conclusions: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI.

Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.

Background: Exosomes derived from the bone marrow mesenchymal stem cell (MSC) have shown great potential in spinal cord injury (SCI) treatment. This research was designed to investigate the therapeutic effects of miR-26a-modified MSC-derived exosomes (Exos-26a) following SCI. Methods: Bioinformatics and data mining were performed to explore the role of miR-26a in SCI. Exosomes were isolated from miR-26a-modified MSC culture medium by ultracentrifugation. A series of experiments, including assessment of Basso, Beattie and Bresnahan scale, histological evaluation, motor-evoked potential recording, diffusion tensor imaging, and western blotting, were performed to determine the therapeutic influence and the underlying molecular mechanisms of Exos-26a in SCI rats. Results: Exos-26a was shown to promote axonal regeneration. Furthermore, we found that exosomes derived from miR-26a-modified MSC could improve neurogenesis and attenuate glial scarring through PTEN/AKT/mTOR signaling cascades. Conclusions: Exosomes derived from miR-26a-modified MSC could activate the PTEN-AKT-mTOR pathway to promote axonal regeneration and neurogenesis and attenuate glia scarring in SCI and thus present great potential for SCI treatment. Graphical