Aberrantly expressed microRNAs (miRNAs) after spinal cord injury (SCI) participate in diverse biological pathways and processes, including apoptosis, inflammation, oxidative stress responses, peroxidation, and ferroptosis. This study was aimed at exploring the mechanisms underlying miRNA‐mediated ferroptosis in an SCI rat model. In the present study, a T10 weight‐dropping SCI model was established and miRNA profiling was used to detect miRNA expression profiles post‐SCI. Basso‐Beattie‐Bresnahan scores and inclined plane test, hematoxylin and eosin (HE) and Nissl staining, immunohistochemistry and immunofluorescence, western blotting, cell viability, and Annexin V/7‐aminoactinomycin D (7‐AAD) assays were used to evaluate locomotor activity, histological changes in the injured spinal cords, neuronal ferroptosis, ferroptosis suppressor protein 1 (FSP1) expression, and cell death, respectively. It was observed that many miRNAs were differentially expressed after SCI, and miR‐672‐3p, which increased significantly, was selected after cross‐referencing with predicted target miRNAs. The luciferase reporter assay demonstrated that miR‐672‐3p downregulated FSP1, a glutathione‐independent ferroptosis suppressor, by binding to its 3 ^′ untranslated region. Oxygen and glucose deprivation‐ (OGD‐) treated PC12 and AGE1.HN cells were treated with miR‐672‐3p mimics or inhibitors in vitro. The effect of miR‐672‐3p mimics or inhibitor on OGD‐PC12/AGE1.HN ferroptosis was evaluated by flow cytometry, immunohistochemistry, immunofluorescence, and western blotting. The miR‐672‐3p mimics promoted ferroptosis after SCI, whereas the miR‐672‐3p inhibitor inhibited this process. Rats with SCI treated with miR‐672‐3p mimics or inhibitor showed similar results in vivo. Furthermore, the ferroptosis‐related changes caused by SCI or miR‐672‐3p were reversed by overexpression of FSP1 lentivirus in vivo and in vitro. These results indicated that sh‐miR‐672‐3p exerted a neural restoration effect in vivo and in vitro by inhibiting ferroptosis via the FSP1 pathway.

Lithium is associated with oxidative stress and apoptosis, but the mechanism by which lithium protects against spinal cord injury remains poorly understood. In this study, we found that intraperitoneal administration of lithium chloride (LiCl) in a rat model of spinal cord injury alleviated pathological spinal cord injury and inhibited expression of tumor necrosis factor α, interleukin-6, and interleukin 1 β. Lithium inhibited pyroptosis and reduced inflammation by inhibiting Caspase-1 expression, reducing the oxidative stress response, and inhibiting activation of the Nod-like receptor protein 3 inflammasome. We also investigated the neuroprotective effects of lithium intervention on oxygen/glucose-deprived PC12 cells. We found that lithium reduced inflammation, oxidative damage, apoptosis, and necrosis and up-regulated nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 in PC12 cells. All-trans retinoic acid, an Nrf2 inhibitor, reversed the effects of lithium. These results suggest that lithium exerts anti-inflammatory, anti-oxidant, and anti-pyroptotic effects through the Nrf2/heme oxygenase-1 pathway to promote recovery after spinal cord injury. This study was approved by the Animal Ethics Committee of Xi’an Jiaotong University (approval No. 2018-2053) on October 23, 2018.

Persistent inflammation in the secondary spinal cord injury (SCI) is an important reason for the failure of nerve repair, which is partly due to the continuous activation of local M1‐like macrophage/microglia. It is reported that extracellular trap (ET) has been a new way of cell death, which can be released by macrophages and named macrophage extracellular trap (Met). Furthermore, it exists widely in the pathophysiological process of many diseases, but it has been rarely studied in the field of SCI. In this study, we constructed a spinal cord contusion model and assessed the function outcome of SCI rats. We used immunofluorescence, flow cytometry, and transmission electron microscope (TEM) to demonstrate the existence of Mets. Besides, some related experiments had also been employed to explore the relationship between Mets and M1 polarization of macrophage/microglia. We also performed Co‐IP and Western blotting to reveal a new extracellular proinflammatory signal pathway. Finally, we made a linear regression analysis between the concentrations of specific markers of Mets in human serum and ASIA scores. Briefly, our results suggested that macrophages infiltrated in SCI area could induce macrophage/microglia to differentiate into M1‐like cells by releasing Mets, which may be achieved partly through LL37‐P2X37‐NF‐κB signal pathway. However, limiting Mets could effectively inhibit M1 polarization and promote function recovery. In addition, the concentrations of Met related proteins in human serum showed high correlation with ASIA scores and could be applied to reflect the severity of SCI. In conclusion, Mets may be a new target for SCI therapy and a promising index for SCI assessment.

The Cartesian Optoelectronic Dynamic Anthropometer (CODA) motion analysis system is a new instrument that measures 3-dimensional joint movement. The study aimed to investigate the reliability and validity of the CODA motion analysis system in assessing the cervical range of motion in healthy people. A total of 41 healthy participants were included. Movements in 3 planes (flexion and extension, right and left lateral bending, and right and left axial rotation) were measured by using the CODA motion analysis system. The results for flexion-extension and lateral bending movements were compared with those obtained by a standard inclinometer. Intraobserver and interobserver reliability and validity were assessed using the intraclass correlation coefficient (ICC) method. SE of measurement (SEM) and minimal detectable change (MDC) values were also calculated to identify the measurement errors. High interobserver reliability (ICC range, 0.89-0.94) and validity (ICC range, 0.73-0.89) were found for all 3 planes, while the intraobserver reliability (ICC range, 0.76-0.92) was high, except for right lateral bending (ICC, 0.76) and left axial rotation movements (ICC, 0.84). All SEM and MDC values for intraobserver, interobserver, and criterion validity studies were less than 5° and 10°, respectively. Percentage of SEM of ≤10% and percentage of MDC of ≤30% were obtained for all variables. The CODA motion analysis system is a highly reliable, noninvasive, easy-to-use, and reproducible 3-dimensional device for measuring cervical range of motion. It demonstrated good reliability for flexion-extension and lateral bending movements.