The ferroptosis activity is associated with neurological recovery following chronic compressive spinal cord injury

Chronic compressive spinal cord injury in compressive cervical myelopathy conditions can lead to rapid neurological deterioration in the early phase,followed by partial self-recovery,and ultimately an equilibrium state of neurological dysfunction.Ferroptosis is a crucial pathological process in many neurodegenerative diseases;however,its role in chro nic compressive spinal cord injury remains unclear.In this study,we established a chronic compressive spinal cord injury rat model,which displayed its most severe behavioral and electrophysiological dysfunction at 4 wee ks and partial recovery at 8 weeks after compression.Bulk RNA sequencing data identified enriched functional pathways,including ferroptosis,presynapse,and postsynaptic membrane activity at both 4 and 8 wee ks following chro nic compressive spinal co rd injury.Tra nsmission electron microscopy and malondialdehyde quantification assay confirmed that ferroptosis activity peaked at 4 weeks and was attenuated at 8 weeks after chronic compression.Ferro ptosis activity was negatively correlated with behavioral score.Immunofluorescence,quantitative polymerase chain reaction,and western blotting showed that expression of the anti-ferroptosis molecules,glutathione peroxidase 4(GPX4) and MAF BZIP transcription factor G(MafG),in neuro ns was suppressed at 4 weeks and upregulated at 8 weeks following spinal co rd compression.There was a positive correlation between the expression of these two molecules,suggesting that they may work together to contribute to functional recovery following chronic compressive spinal cord injury.In conclusion,our study determined the genome-wide expression profile and fe rroptosis activity of a consistently compressed spinal cord at different time points.The results showed that anti-fe rroptosis genes,specifically GPX4 and MafG,may be involved in spontaneous neurological recovery at 8 weeks of chronic compressive spinal cord injury.These findings contribute to a better understanding of the mechanisms underlying chronic compressive spinal cord injury and may help identify new therapeutic targets for compressive cervical myelopathy.

Does diffusion tensor data reflect pathological changes in the spinal cord with chronic injury?

Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy poly- urethane material was implanted in the rat C^-s epidural space to establish a rat model of chronic cervical spondylotic myelopathy. Diffusion tensor data were used to predict pathological changes. Results revealed that the fractional anisotropy value gradually decreased at 4, 24, and 72 hours and 1 week after injury in rat spinal cord, showing a time-dependent manner. Average diffusion coeffi- cient increased at 72 hours and 1 week after implantation. Hematoxylin-eosin staining and Luxol-fast-blue staining exhibited that the number of neurons in the anterior horn of the spinal cord gray matter and the nerve fiber density of the white matter gradually reduced with prolonged com- pression time. Neuronal loss was most significant at 1 week after injury. Results verified that the fractional anisotropy value and average diffusion coefficient reflected the degree of pathological change in the site of compression in rat models at various time points after chronic spinal cord compression injury, which potentially has a reference value in the early diagnosis of chronic cervical spondylotic myelopathy.