• Xuegang He, Bo Deng, Miao Ma, Keyao Wang, Ying Li, Yonggang Wang, and Xuewen Kang.
• Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, China; The Second Clinical Medical College, Lanzhou University, Lanzhou, China; The International Cooperation Base of Gansu Province for the Pain Research in Spinal Disorders, Lanzhou, China.
• World Neurosurg. 2023 Jun 20.

BackgroundProgrammed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies.MethodsWe downloaded the rats' SCI expression matrix GSE45006, and the ssGSEA method was used to analyze the PCD after SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction, and HUB genes were identified. Finally, the correlation between HUB genes and PCD was analyzed.ResultsApoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy increased significantly in acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury, and autophagy.ConclusionsPCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, and ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related HUB genes may be the therapeutic target of SCI.Copyright © 2023 Elsevier Inc. All rights reserved.

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