{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:07:43Z","timestamp":1790140063239,"version":"4.0.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Copper homeostasis imbalance is closely linked to the progression of various neurological disorders. Cuproptosis, a recently identified form of cell death caused by abnormal intracellular copper accumulation, has an unclear relationship with hypoxic\u2013ischemic brain damage (HIBD). This study aims to characterize cuproptosis-associated molecular changes in the pathological process of HIBD in neonatal rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A neonatal rat HIBD model was established using the modified Rice\u2013Vannucci method. Cerebral blood flow was measured with laser Doppler flowmetry, while infarct volume was assessed through 2,3,5-triphenyltetrazolium chloride staining. To evaluate brain tissue damage and mitochondrial ultrastructural changes, histological staining and transmission electron microscopy were utilized. Specific assay kits were used to detect oxidative stress markers and copper ion levels in the brain tissue. Immunofluorescence staining was employed to monitor DLAT expression in neural cells, and Western blotting was conducted to analyze the expression of cuproptosis-related proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared to the Sham group, the HIBD group exhibited significantly reduced perfusion in the injured cerebral hemisphere, which was associated with liquefactive necrosis and tissue atrophy. Additionally, increased levels of copper ions and ROS, along with decreased levels of GSH and GPX4, indicated that HIBD leads to copper dyshomeostasis and oxidative stress. Staining results showed glial cell activation, neuronal loss, and widespread downregulation of DLAT expression in the HIBD group, suggesting the presence of neuroinflammatory responses and cellular metabolic disturbances. Furthermore, the upregulation of cuproptosis-related proteins FDX1 and HSP70, along with the downregulation of LIAS, ACO2, and Lip-DLAT, and such molecular changes correlate with impaired lipoylation metabolism and iron\u2013sulfur cluster biosynthesis, aligning with molecular signatures of cuproptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies multiple cuproptosis-related molecular alterations coinciding with neuronal injury after HIBD in neonatal rats; these changes are accompanied by impaired lipoylation modification and disrupted redox homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1855158","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:48:06Z","timestamp":1790138886000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cuproptosis-related molecular alterations in a neonatal rat model of hypoxic\u2013ischemic brain damage"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiqi","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaochun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"10020","DOI":"10.1007\/s12035-025-04896-4","article-title":"Preconditioning and posttreatment strategies in neonatal hypoxic-ischemic encephalopathy: recent advances and clinical 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