{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:05:12Z","timestamp":1789362312163,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"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. Mol. Biosci."],"abstract":"<jats:p>\n                    Intracerebral hemorrhage (ICH) causes severe neurological deficits, and secondary neuronal injury is a major barrier to recovery. Cuproptosis, a copper-dependent form of regulated cell death, has been linked to metabolic stress, but its role in axonal injury after ICH remains unclear. Here, we used\n                    <jats:italic>in vivo<\/jats:italic>\n                    rat ICH models and\n                    <jats:italic>in vitro<\/jats:italic>\n                    ICH-like neuronal injury models to examine changes in copper homeostasis, cuproptosis-associated molecular alterations, and axonal injury following ICH. Copper levels were markedly increased in perihematomal brain tissue and injured neurons, accompanied by reduced mitochondrial protein lipoylation and increased dihydrolipoamide S-acetyltransferase oligomerization, consistent with cuproptosis-associated molecular abnormalities. Specificity protein 1 (Sp1) and the copper transporter 1 (CTR1) were also significantly upregulated and showed similar temporal patterns. In parallel, ICH induced axonal injury-related molecular changes, including increased amyloid precursor protein and decreased growth-associated protein 43 expression. Pharmacological inhibition of Sp1 with plicamycin reduced CTR1 expression, attenuated copper overload, ameliorated cuproptosis-associated molecular abnormalities, and improved the measured axonal injury-related molecular and morphological changes\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . These findings suggest that Sp1\/CTR1-associated copper uptake regulation may contribute to secondary neuronal injury after ICH and may represent a potential therapeutic entry point for further investigation.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2026.1932767","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:35:41Z","timestamp":1789360541000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of the Sp1\/CTR1 axis attenuates cuproptosis and alleviates axonal injury following intracerebral hemorrhage"],"prefix":"10.3389","volume":"13","author":[{"given":"Ke","family":"Zhang","sequence":"first","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Ma","sequence":"additional","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Likun","family":"Wang","sequence":"additional","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]},{"name":"Key Lab of Acute Brain Injury and Function Repair in Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]},{"name":"Key Lab of Acute Brain Injury and Function Repair in Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjun","family":"Song","sequence":"additional","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]},{"name":"Key Lab of Acute Brain Injury and Function Repair in Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Ren","sequence":"additional","affiliation":[{"name":"Emergency Department, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]},{"name":"Key Lab of Acute Brain Injury and Function Repair in Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s11910-023-01282-2","article-title":"Neuroinflammation in acute ischemic and hemorrhagic stroke","volume":"23","author":"Alsbrook","year":"2023","journal-title":"Curr. 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