机构地区:[1]Department of Spine Surgery,Orthopedics Center of Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong Province,China [2]Department of Spine Surgery,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong Province,China [3]Department of Gastroenterology,Guangzhou Women and Children’s Medical Center,Jinan University,Guangzhou,Guangdong Province,China [4]Department of Spine Surgery,Zhujiang Hospital,Southern Medical University,Guangzhou,Guangdong Province,China
出 处:《Neural Regeneration Research》2023年第11期2482-2488,共7页中国神经再生研究(英文版)
摘 要: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 spi
关 键 词:chronic spinal cord compression compressive cervical myelopathy ferroptosis genome-wide transcriptome glutathione peroxidase 4(GPX4) MAF BZIP transcription factor G(MafG) neurological function
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