{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:18:10Z","timestamp":1788441490551,"version":"build-2803163510"},"reference-count":45,"publisher":"IMR Press","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82472534"],"award-info":[{"award-number":["82472534"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82502979"],"award-info":[{"award-number":["82502979"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Natural Science Foundation","award":["L2510029"],"award-info":[{"award-number":["L2510029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background:Distractive spinal cord injury (DSCI), a severe complication of spinal deformity correction surgery, is characterized by rapid neuronal loss. However, the molecular mechanisms linking mechanical distraction to apoptosis remain unclear. Here, we tested whether sodium rutin (NaR), a water-soluble rutin derivative with improved oral bioavailability, mitigates DSCI.Methods:We employed an in vivo rat DSCI model and an in vitro mechanical distraction (DIS) model using neuronal cells. The therapeutic efficacy of NaR was evaluated using locomotor function assessments (Basso\u2013Beattie\u2013Bresnahan score and footprint analysis), histopathology, and transmission electron microscopy. Molecular docking simulations were performed to predict the binding affinity of NaR to Erb-B2 receptor tyrosine kinase 4 (ErbB4). Mechanistic investigations targeting the ErbB4\/protein kinase B (Akt) axis, reactive oxygen species (ROS), and apoptotic pathways were conducted using western blot analysis and immunofluorescence.Results:DIS suppressed ErbB4 phosphorylation and downstream Akt signaling, accompanied by the activation of B-cell lymphoma 2\/Bcl-2-associated X protein\/Caspase-3 (Bcl-2\/Bax\/Caspase-3) apoptotic pathways after DSCI. Simultaneously, DIS induced a decrease in the mitochondrial membrane potential (\u0394\u03a8m) and accumulation of mitochondrial ROS, along with a significant reduction in superoxide dismutase 2 (SOD2) and glutathione peroxidase 4 (GPX4) levels. NaR treatment engaged ErbB4 to restore ErbB4\/Akt signaling, inhibited mitochondrial ROS signaling, ameliorated \u0394\u03a8m, and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic neurons, thereby inhibiting neuronal apoptosis. However, the inhibition of ErbB4 phosphorylation along with NaR treatment significantly reversed these therapeutic effects. Furthermore, the pharmacological administration of NaR ameliorated histopathological and neuronal ultrastructural damage in the spinal cord tissues, increased the number of surviving neurons, and facilitated locomotor recovery after DSCI.Conclusions:These findings identify ErbB4 and ROS signaling as key regulators of neuronal survival during DSCI and establish NaR as a candidate therapeutic strategy for DSCI associated with spinal deformity correction surgery.<\/jats:p>","DOI":"10.31083\/jin51000","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:51:46Z","timestamp":1788439906000},"source":"Crossref","is-referenced-by-count":0,"title":["Sodium Rutin Alleviates Neuronal Apoptosis and Promotes Locomotor Recovery in Distractive Spinal Cord Injury via ErbB4 and ROS Signaling"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-6504","authenticated-orcid":true,"given":"Weishi","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"},{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7352-8354","authenticated-orcid":true,"given":"Yeqiu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"},{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3263-3518","authenticated-orcid":true,"given":"Junrui Jonathan","family":"Hai","sequence":"additional","affiliation":[{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"},{"name":"Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2374-2756","authenticated-orcid":true,"given":"Duan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"},{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8254-8567","authenticated-orcid":true,"given":"Yihan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"},{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1738-3828","authenticated-orcid":true,"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9984-7663","authenticated-orcid":true,"given":"Peng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China"},{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-0497","authenticated-orcid":true,"given":"Yajin","family":"Liao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Neurodegenerative diseases (University of South China), 421001 Hengyang, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-5700","authenticated-orcid":true,"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"},{"name":"Department of Spinal Surgery, Beijing Jishuitan Hospital, Capital Medical University, 100035 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-3490","authenticated-orcid":true,"given":"Xianjun","family":"Qu","sequence":"additional","affiliation":[{"name":"Joint Laboratory for Research & Treatment of Spinal Cord Injury in Spinal Deformity, Capital Medical University, 100069 Beijing, China"},{"name":"Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, 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