{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T18:34:15Z","timestamp":1777833255489,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T00:00:00Z","timestamp":1762041600000},"content-version":"vor","delay-in-days":1,"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":["82170589"],"award-info":[{"award-number":["82170589"]}],"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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microglial overactivation\u2010driven neuroinflammation exacerbates secondary damage after spinal cord injury (SCI), but the role of mitochondrial iron metabolism in this process is not well understood. This study investigates the function of the mitochondrial iron transporter solute carrier family 25 member 28 (SLC25A28) in post\u2010SCI neuroinflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Microglia\u2010specific SLC25A28 knockout (A28\u2010MGKO) mice were generated by crossing SLC25A28\n                      <jats:sup>flox\/flox<\/jats:sup>\n                      mice with Cx3cr1\u2010CreERT2 mice and subjected to clip\u2010compression spinal cord injury (SCI) at the T9 level. Motor recovery was evaluated using the Basso Mouse Scale (BMS), while histological and biochemical assessments including hematoxylin\u2013eosin and Nissl staining, Iba1 immunohistochemistry, Evans blue permeability, and tissue water content were performed to evaluate lesion severity, neuronal survival, microglial activation, and blood\u2013spinal cord barrier integrity. In\u00a0vitro, primary microglia isolated from A28\u2010MGKO mice and BV2 cells with SLC25A28 overexpression were used to investigate mitochondrial iron homeostasis, heme biosynthesis, and NOX2\u2010mediated oxidative stress. Mitochondrial iron content was quantified using a ferrozine\u2010based assay and Mito\u2010FerroGreen staining, while ROS production, cytokine release, and inflammatory signaling were analyzed by fluorescence imaging, ELISA, and Western blotting under pharmacological modulation of heme synthesis and NOX2 activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that SLC25A28 deficiency reduced spinal cord edema, blood\u2010spinal cord barrier disruption, and motor deficits. Mechanistically, SLC25A28 knockout suppressed mitochondrial iron accumulation, inhibited heme synthesis, and reduced NOX2\u2010mediated oxidative stress. However, SLC25A28 overexpression enhanced mitochondrial iron overload and NOX2\u2010driven inflammation, which could be reversed by pharmacological blockade of NOX2 or heme synthesis. Restoration of heme synthesis in A28\u2010MGKO microglia attenuated the anti\u2010inflammatory effects of SLC25A28 knockout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that microglial SLC25A28 regulates neuroinflammation and functional recovery after SCI by promoting mitochondrial iron\u2010dependent heme synthesis and NOX2 activation. Targeting the SLC25A28\u2013heme\u2013NOX2 axis may provide a novel therapeutic approach for SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70638","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:01:22Z","timestamp":1762146082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Microglial\n                    <scp>SLC25A28<\/scp>\n                    Knockout Mitigates Spinal Cord Injury in Mice by Inhibiting Heme Synthesis and Subsequent\n                    <scp>NOX2<\/scp>\n                    Activation"],"prefix":"10.1111","volume":"31","author":[{"given":"Huangtao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital of Xi'an Jiao Tong University  Xi'an Shaanxi 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