{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:14:01Z","timestamp":1779804841136,"version":"3.53.1"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathological mechanisms after spinal cord injury (SCI) are complex, making SCI repair a major clinical challenge for clinical treatment. Currently, there is no effective method to effectively improve the prognosis of patients. A deeper understanding of post\u2010SCI pathology may reveal new targets and strategies for clinical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A rat SCI model was constructed, and HE staining, immunohistochemistry, and tissue immunofluorescence double staining were used to detect the pathological changes and cell death in injured tissue. Human astrocytes were subjected to hypoxic conditions, and necroptosis and apoptosis mechanisms were investigated using CCK8, immunofluorescence, Western blot, transmission electron microscopy, and related assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo animal experiments demonstrated that after SCI, rats exhibited the formation of damage cavities and increased astrocyte apoptosis in the lesion area, along with significantly elevated expression of key proteins in the HIF\u20101\u03b1 pathway and necroptosis. In\u00a0vitro cellular experiments showed that hypoxia induced the elevation of the expression of key factors of human astrocytes HIF1\u03b1 and JAK\/STAT, necroptosis, and the conversion of the cells to an A1\u2010type phenotype with the use of the necroptosis inhibitors, JAK\/STAT inhibitors or knockdown of HIF1\u03b1 or knockdown of RIP1 expression could reverse the hypoxia\u2010induced effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, hypoxia promotes COI formation after SCI by activating the HIF\u20101\u03b1\u2013JAK\u2013STAT pathway, which in turn leads to necroptosis of astrocytes.<\/jats:p>\n                  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