{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:22:23Z","timestamp":1787775743210,"version":"build-2784847793"},"reference-count":73,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202602000-00041\/figure1\/v\/2026-04-22T115157Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage. Neuronal ferroptosis in particular plays an important role in early brain injury. Bromodomain-containing protein 4, a member of the bromo and extraterminal domain family of proteins, participated in multiple cell death pathways, but the mechanisms by which it regulates ferroptosis remain unclear. The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons, and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . In addition, ferroptosis-related pathways were activated\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    after subarachnoid hemorrhage. Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis. Using cleavage under targets and tagmentation analysis, we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . Furthermore, treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074, a Raf-1 inhibitor, exacerbated neuronal ferroptosis by suppressing the Raf-1\/ERK1\/2 signaling pathway. Moreover, targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage. Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage, and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-24-00147","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T08:48:57Z","timestamp":1722934137000},"page":"715-729","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":3,"title":["Bromodomain-containing protein 4 knockdown promotes neuronal ferroptosis in a mouse model of subarachnoid hemorrhage"],"prefix":"10.4103","volume":"21","author":[{"given":"Peng","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"He","sequence":"additional","affiliation":[{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Kong","sequence":"additional","affiliation":[{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Institute of Brain Science, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kecheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuke","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangfan","family":"Xie","sequence":"additional","affiliation":[{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Institute of Brain Science, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Institute of Brain Science, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Sichuan Clinical Research Center for Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Institute of Brain Science, Southwest Medical University, Luzhou, Sichuan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3348-9538","authenticated-orcid":false,"given":"Jianhua","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Laboratory of Neurological Diseases and Brain Function, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, China"},{"name":"Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, 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