{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:14:38Z","timestamp":1778645678424,"version":"3.51.4"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["82302877"],"award-info":[{"award-number":["82302877"]}],"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":["82172541"],"award-info":[{"award-number":["82172541"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30549"],"award-info":[{"award-number":["2023JJ30549"]}],"id":[{"id":"10.13039\/501100004735","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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Traumatic spinal cord injury (SCI) induces neuronal apoptosis and neuroinflammation, which exacerbate secondary damage and hinder functional recovery. Efficient clearance of apoptotic cells and modulation of the inflammatory microenvironment of spinal cord are essential for promoting tissue repair. This study aimed to investigate whether Midkine (MDK), a heparin\u2010binding growth factor, facilitates functional recovery after SCI and explores the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A rat model of moderate SCI was established using Allen's impact method. Lentiviral vectors were used to overexpress MDK in the spinal cord. Behavioral assessments, including BBB score and gait analysis, were performed to evaluate motor function recovery. Motor evoked potentials (MEPs) serve as a neurophysiological tool for evaluating the functional integrity of the corticospinal tract. In\u00a0vivo and in\u00a0vitro experiments were conducted to assess microglial efferocytosis and elucidate the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic bioinformatic analysis suggests that SCI is characterized by pronounced accumulation of apoptotic cells and robust neuroinflammatory responses, whereas single\u2010cell analysis implicates MDK as a key contributor to neurorepair after SCI. MDK expression is dynamically regulated following SCI, with an early upregulation followed by a gradual decline over time, its location predominantly observed around microglial cells. Functionally, MDK overexpression significantly enhances motor recovery after SCI, accompanied by reduced neuroinflammation, decreased neuronal apoptosis, and improved neuroprotection. Mechanistically, MDK promotes microglial efferocytosis both in\u00a0vivo and in\u00a0vitro, activates the AKT\/mTOR signaling pathway, upregulates BDNF and LRP\u20101 expression, and facilitates microglial polarization toward an anti\u2010inflammatory M2 phenotype. Notably, inhibition of LRP\u20101 with receptor\u2010associated protein (RAP) abolished the efferocytic and neuroprotective effects of recombinant MDK, highlighting LRP\u20101 as a key mediator of MDK's actions in microglia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study unveils the MDK\/LRP\u20101\/efferocytosis axis as a previously unrecognized therapeutic target for SCI. By orchestrating apoptotic cell clearance, dampening neuroinflammation, and fostering neuroprotection, this axis critically shapes the post\u2010injury microenvironment to facilitate recovery. These findings suggest that MDK\u2010centered therapy may represent a strategy for spinal cord repair, with LRP\u20101 modulation offering precise control over microglial responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70841","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:17:22Z","timestamp":1773926242000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Midkine Overexpression Promotes Functional Recovery After Spinal Cord Injury by Enhancing Microglial Efferocytosis Via\n                    <scp>LRP<\/scp>\n                    \u20101"],"prefix":"10.1002","volume":"32","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Rehabilitation Medicine Center The First Affiliated Hospital With Nanjing Medical University  Nanjing 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