{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:48:48Z","timestamp":1793386128167,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012546","name":"Chongqing Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["CSTB2023NSCQ\u2010BHX0046"],"award-info":[{"award-number":["CSTB2023NSCQ\u2010BHX0046"]}],"id":[{"id":"10.13039\/100012546","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012546","name":"Chongqing Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["CSTB2023NSCQ\u2010BHX0068"],"award-info":[{"award-number":["CSTB2023NSCQ\u2010BHX0068"]}],"id":[{"id":"10.13039\/100012546","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82402983"],"award-info":[{"award-number":["82402983"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Ferroptosis is a distinct form of cell death characterized by iron\u2010dependent lipid peroxidation and plays a crucial role in the early brain injury (EBI) following subarachnoid hemorrhage (SAH). As a newly discovered endogenous ligand for the C\u2010KIT receptor tyrosine kinase, meteorin\u2010like protein (Metrnl) exerts regulatory functions in oxidative stress and protects against various diseases. However, the specific role of the Metrnl\/C\u2010KIT axis in neuronal ferroptosis during EBI following SAH remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sprague Dawley rats were used to establish the SAH model through endovascular perforation. r\u2010Metrnl was administered intranasally 1\u2009h after SAH. Metrnl shRNA, C\u2010KIT inhibitor ISCK03, AMPK inhibitor dorsomorphin, and Nrf2 inhibitor ML385 were administered intracerebroventricularly or intraperitoneally before r\u2010Metrnl treatment to explore the underlying mechanisms. Neurobehavioral assessments, immunofluorescence, western blot, ELISA, Fluoro\u2010Jade C staining, transmission electron microscopy, and Nissl staining were conducted to evaluate the effects. Additionally, primary neuron culture with hemoglobin (Hb) stimulation was used for in\u00a0vitro studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Phosphorylated C\u2010KIT and endogenous Metrnl levels were upregulated after SAH. Knockdown of Metrnl aggravated neurobehavioral deficits and neuronal ferroptosis, whereas r\u2010Metrnl treatment showed a protective effect. Mechanistically, r\u2010Metrnl significantly increased the protein levels of SLC7A11, GPX4, FTH, FSP1, and GSH, whereas it decreased the levels of ACSL4, 4HNE, and MDA in the ipsilateral hemisphere 24\u2009h after SAH. Also, r\u2010Metrnl reduced mitochondrial shrinkage, increased mitochondrial crista, and decreased membrane density. However, the beneficial effects of r\u2010Metrnl were partially reversed by ISCK03, dorsomorphin, or ML385 treatment both in\u00a0vivo and in\u00a0vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study demonstrated that r\u2010Metrnl reduced neuronal ferroptosis and improved neurological outcomes after SAH by modulating the C\u2010KIT\/AMPK\/Nrf2 signaling pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70286","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:42:24Z","timestamp":1740120144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Metrnl\/C\u2010KIT Axis Attenuates Early Brain Injury Following Subarachnoid Hemorrhage by Inhibiting Neuronal Ferroptosis"],"prefix":"10.1111","volume":"31","author":[{"given":"You","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The Second Affiliated Hospital Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital Chongqing Medical University  Chongqing 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