{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T11:13:45Z","timestamp":1782645225155,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271252"],"award-info":[{"award-number":["82271252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204542"],"award-info":[{"award-number":["82204542"]}],"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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Many studies have emphasized the role of microglia\u2010mediated neuroinflammation in spinal cord injury (SCI); however, effective clinical targets remain elusive. The growth arrest\u2010specific 6 (Gas6)\/Axl receptor tyrosine kinase (Axl) signaling pathway has been implicated in reducing inflammation, promoting tissue repair, and functional recovery. Here, we elucidate the importance of the Gas6\u2010Axl signaling pathway in SCI repair and evaluate the role of bilirubin in modulating Gas6\u2010Axl signaling after SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SCI mice model was used to investigate the effects of bilirubin treatment on inflammation and motor function recovery. Additionally, Gas6\u2010deficient (\n                      <jats:italic>Gas6<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>\/<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      ) mice and wild\u2010type (WT) mice were employed to examine the role of Gas6\u2010Axl signaling in SCI recovery. Microglial cells were cultured to assess the effects of bilirubin on the activation of the Gas6\u2010Axl\u2010SOCS3 signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Gas6<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>\/<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice exhibited increased mortality, severe locomotor deficits, and impaired neuromuscular activity compared to WT mice. Bilirubin treatment in SCI models facilitated recovery by upregulating Gas6\u2010Axl signaling, which in turn enhanced SOCS3 expression and suppressed the expression of pro\u2010inflammatory mediators such as IL\u20101\u03b2 and MMP\u20109. Furthermore, bilirubin treatment reduced microglial activation, highlighting its neuroprotective and anti\u2010inflammatory properties.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study underscores the importance of the Gas6\u2010Axl\u2010SOCS3 axis in regulating functional recovery and inflammation after SCI. Activation of the Gas6\u2010Axl pathway, particularly when combined with bilirubin treatment, represents a promising therapeutic strategy for mitigating SCI\u2010induced damage and improving functional outcomes. Given their central role in both the pathogenesis and resolution of SCI, bilirubin treatment emerges as a promising clinical therapeutic drug for SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70538","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T07:27:22Z","timestamp":1758094042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bilirubin Alleviates Spinal Cord Injury by Enhancing\n                    <scp>SOCS3<\/scp>\n                    \u2010Mediated Anti\u2010Inflammatory Effects via Gas6\u2010Axl Signaling"],"prefix":"10.1111","volume":"31","author":[{"given":"Kun\u2010Mao","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Qi","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Ting","family":"Qi","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine Center The First Afliated Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-7927","authenticated-orcid":false,"given":"Wen\u2010Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong\u2010Tong","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture Nanjing University of Chinese Medicine  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Yong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Shandong First Medical University &amp; 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