{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:24:13Z","timestamp":1787297053369,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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":["82401498"],"award-info":[{"award-number":["82401498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Traumatic spinal cord injury (SCI) induces a robust local inflammatory response that can both facilitate repair and exacerbate pathology. Hydroxycarboxylic acid receptor 2 (Hcar2) is known to exert immunomodulatory effects; however, its role in SCI and its potential for targeting Hcar2 to alleviate motor deficits remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The spinal cord transcriptome following SCI, with a focus on\n                      <jats:italic>Hcar2<\/jats:italic>\n                      , was analysed via publicly available single\u2010cell RNA sequencing datasets from mice and rhesus macaques. Additionally, an in vivo SCI mouse model with\n                      <jats:italic>Hcar2<\/jats:italic>\n                      knockout and an in vitro LPS\u2010induced BV2 microglial model were established to assess\n                      <jats:italic>Hcar2<\/jats:italic>\n                      gene and protein expression, microglial activation and inflammatory responses via bulk RNA sequencing, immunofluorescence staining, Western blotting, and real\u2010time polymerase chain reaction. To evaluate the protective effects of Hcar2 activation, niacin, a known Hcar2 agonist, was administered to mice or BV2 cells, followed by assessments of the inflammatory response and motor function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Hcar2<\/jats:italic>\n                      gene expression, which was enriched predominantly in spinal cord microglia, was upregulated following SCl, peaking at 7 days post\u2010SCl. Genetic knockout of\n                      <jats:italic>Hcar2<\/jats:italic>\n                      decreased the percentage of impaired anti\u2010inflammatory polarized microglia and increased the inflammatory response. In contrast, Hcar2 activation with niacin in LPS\u2010stimulated microglia BV cell models reversed mitochondrial dysfunction, increased the oxygen consumption rate and reduced the expression of the cytokines\n                      <jats:italic>IL\u20106<\/jats:italic>\n                      and\n                      <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                      . The administration of niacin to SCl mice upregulated anti\u2010inflammatory microglia, reduced the expression of multiple proinflammatory cytokines, increased the number of motor neurons and improved motor function recovery. Notably, all these protective effects were abolished by genetic loss of\n                      <jats:italic>Hcar2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hcar2 serves as a critical regulator of microglial polarization, promoting the switch from a proinflammatory phenotype to an anti\u2010inflammatory phenotype through immunometabolic reprogramming. Targeting Hcar2 with niacin may offer a translatable therapeutic strategy to improve functional recovery after SCl.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Hcar2 is identified as a conserved, injury\u2010induced metabolic checkpoint specifically enriched in microglia following spinal cord injury.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hcar2 activation reprogrammes microglial metabolism from glycolysis to oxidative phosphorylation to drive reparative anti\u2010inflammatory polarization.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological targeting of Hcar2 with niacin resolves neuroinflammation and promotes functional motor recovery in an Hcar2\u2010dependent manner.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70683","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T06:16:50Z","timestamp":1777702610000},"source":"Crossref","is-referenced-by-count":0,"title":["Niacin promotes motor function recovery after spinal cord injury via Hcar2\u2010dependent microglia immunometabolic regulation"],"prefix":"10.1002","volume":"16","author":[{"given":"Hua","family":"Du","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingnian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huyao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents\u2019 Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders  Chongqing 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