{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:32:29Z","timestamp":1786977149333,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ferroptosis in pathophysiological mechanisms in early brain injury after subarachnoid hemorrhage (SAH\u2010EBI) has been demonstrated. MicroRNAs (miRNAs) are involved in various aspects of neurological disorders. A growing number of studies suggest that intense inflammation mediated by M1 microglia after subarachnoid hemorrhage (SAH) may lead to neurological damage. According to our research and related reports, exosomal miR\u2010369\u20103p is involved in the pathophysiological process of SAH, and miR\u2010369\u20103p has a potentially central role in regulating inflammatory responses. Therefore, targeted delivery of miR\u2010369\u20103p across the blood\u2010brain barrier (BBB) into the brain to alleviate SAH\u2010EBI is a promising therapeutic approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we extracted exosomes from RBCs and then modified RVG peptide onto the exosome surface using the click chemistry principle. Finally, miR\u2010369\u20103p mimic was loaded into the RVG peptide\u2010modified exosomes to form RVG\u2010Exo\/miR\u2010369\u20103p (RVG\u2010Exo\/miR) by electroporation. Tail vein injection of RVG\u2010Exo\/miR was used to achieve delivery of miR\u2010369\u20103p into the brain of SAH mice. The effect of miR\u2010369\u20103p on SAH\u2010EBI was examined by neurobehavioral scores, brain water content, Fluoro\u2010Jade C (FJC) staining, and Nissl staining. MDA and GSH kits were used to assess the extent of ferroptosis occurrence. Western blotting analysis, immunofluorescence staining, and qRT\u2010PCR were used to detect the levels of each protein, mRNA, and miRNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The exosome system (RVG\u2010Exo\/miR) successfully delivered miR\u2010369\u20103p to the mouse central nervous system across the blood\u2010brain barrierBBB. This exosomal system reduced the number of M1 microglia by enhancing their sensitivity to ferroptosis by inhibiting the expression of iNOS and GPX4. In addition, miR\u2010369\u20103p treatment alleviated neurobehavioral disorders, brain edema, and neuronal damage after SAH\u2010EBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>RVG\u2010Exo\/miR promotes ferroptosis in M1 microglia by inhibiting the iNOS\/GPX4 axis, which may be a new and effective therapeutic strategy for treating SAH\u2010EBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70966","type":"journal-article","created":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:16:38Z","timestamp":1760242598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exosomes miR\u2010369\u20103p Alleviates Early Brain Injury After Subarachnoid Hemorrhage by Promoting Ferroptosis of M1 Microglia via Inhibiting iNOS\/GPX4 Axis"],"prefix":"10.1002","volume":"15","author":[{"given":"Jian","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Translational Research Institute for Neurological Disorders of Wannan Medical College The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Translational Research Institute for Neurological Disorders of Wannan Medical College The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College)  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Xu","sequence":"additional","affiliation":[{"name":"The Institutes of Brain Science Wannan Medical College  Wuhu Anhui 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