{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:41:31Z","timestamp":1793374891088,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803536; 82171351"],"award-info":[{"award-number":["81803536; 82171351"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Microglial HO\u20101 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co\u2010located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a\/ATG\u2010mediated autophagy and HO\u20101 signalling resulting in ferroptosis in\u00a0vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf\u2010A1 or HO\u20101 inhibitor ZnPP protected against hemin\u2010induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a\/ATG\u2010mediated autophagy and HO\u20101 signalling pathway. Knock\u2010down of FoxO3a inhibited autophagy and prevented hemin\u2010induced ferroptosis dependent of HO\u20101 signalling. We first showed that hemin stimulated microglial FoxO3a\/HO\u20101 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro\u2010inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis\u2010induced striatum injury in the autologous blood\u2010induced ICH model. We demonstrate, for the first time, that FoxO3a\/ATG\u2010mediated autophagy and HO\u20101 play an important role in microglial activation and ferroptosis\u2010induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.<\/jats:p>","DOI":"10.1111\/jcmm.18007","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T19:45:40Z","timestamp":1698435940000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Microglial <scp>FoxO3a<\/scp> deficiency ameliorates ferroptosis\u2010induced brain injury of intracerebral haemorrhage via regulating autophagy and heme oxygenase\u20101"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-8147","authenticated-orcid":false,"given":"Rikang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Peking University Shenzhen Hospital  Shenzhen 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