{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:15:34Z","timestamp":1789236934397,"version":"build-2803163510"},"reference-count":35,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event characterized by early brain injury (EBI) within 72 h that is driven by oxidative stress, mitochondrial dysfunction, and metabolic collapse. The retinoic acid receptor-related orphan receptor alpha (ROR\u03b1) is a nuclear receptor implicated in metabolic and inflammatory regulation, but it has not been studied in SAH. We aimed to determine whether ROR\u03b1 confers neuroprotection after SAH and to elucidate its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      We used mouse SAH models and primary cortical neurons to assess the ROR\u03b1 expression, functional outcomes, and metabolic changes. The ROR\u03b1 expression was markedly reduced post-SAH. Genetic knockdown or deficiency (staggerer mice) exacerbated neuronal apoptosis, neuroinflammation, and behavioral deficits. Conversely, pharmacological activation with SR1078 significantly improved neurological scores, preserved neuronal morphology, and reduced oxidative stress. ROR\u03b1 overexpression or SR1078 treatment enhanced neuronal viability\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      under hemoglobin-induced stress. Transcriptomic and epigenomic profiling revealed that ROR\u03b1 directly regulated glucose-6-phosphate dehydrogenase and \u03b1 subunit of peroxisome proliferator activated receptor-\u03b3 coactivator-1. This promoted pentose phosphate pathway flux and mitochondrial biogenesis. A metabolic flux analysis confirmed increased nicotinamide adenine dinucleotide phosphate hydrogen and glutathione synthesis, reduced reactive oxygen species accumulation, and an improved oxygen consumption rate and spare respiratory capacity. All of these results indicated a shift toward oxidative phosphorylation and enhanced bioenergetics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      We are the first to demonstrate that ROR\u03b1 activation reprogrammed neuronal glucose metabolism and strengthened antioxidant defenses to mitigate SAH-induced EBI. The targeting of ROR\u03b1 could represent a promising therapeutic strategy for stroke-related metabolic failure and oxidative stress. Future work should explore the translational potential in clinical settings.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      44, 275\u2013291.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864251399609","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T15:19:57Z","timestamp":1764775197000},"page":"275-291","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Retinoic Acid Receptor-related Orphan Receptor \u03b1 Drives Glucose Reprogramming and Mitochondrial Rescue Mitigate Subarachnoid Hemorrhage-Induced Early Brain Injury"],"prefix":"10.1177","volume":"44","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Ministry of Education, Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Ministry of Education, Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijing","family":"Guo","sequence":"additional","affiliation":[{"name":"Anatomy Teaching and Research Office, Guangzhou University of Traditional Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichao","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."},{"name":"Ministry of Education, Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"e_1_3_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyx364"},{"key":"e_1_3_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-024-00455-z"},{"key":"e_1_3_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03708.x"},{"key":"e_1_3_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0307-z"},{"key":"e_1_3_5_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.117.017758"},{"key":"e_1_3_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103139"},{"key":"e_1_3_5_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-016-1193-9"},{"key":"e_1_3_5_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a015008"},{"issue":"16","key":"e_1_3_5_10_1","first-page":"1935","article-title":"Neuroprotective effects of Edaravone on early brain injury in rats after subarachnoid hemorrhage","volume":"122","author":"Gao Y","year":"2009","unstructured":"Gao Y, , Ding XS, , Xu S, et al. 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