Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

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.