{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:59:14Z","timestamp":1791561554809,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["82305381"],"award-info":[{"award-number":["82305381"]}],"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":["82374593"],"award-info":[{"award-number":["82374593"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Beyond the primary lesion, spinal cord injury (SCI) induces secondary neuroinflammation in the frontal cortex, a critical factor exacerbating neural damage and impeding functional recovery. This remote inflammatory response is predominantly regulated by the HMGB1\/TLR4 signaling pathway. While electroacupuncture (EA) shows therapeutic promise, whether its efficacy is causally dependent on modulating this supraspinal inflammation remains unproven. This study investigated whether EA promotes functional recovery by suppressing the HMGB1\/TLR4\/NF\u2010\u03baB pathway in the frontal cortex of rats with SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One hundred and fifty adult male rats were randomly assigned to Sham, SCI, EA, SCI+ HMGB1 Inhibitor (I), and SCI + EA + HMGB1 Inhibitor (EA + I) groups. Functional recovery was assessed at 1, 7, 14, and 28 days post\u2010SCI using Basso, Beattie, and Bresnahan (BBB) scores and the inclined plate test. Frontal cortex tissue was analyzed at 7, 14, and 28 days post\u2010injury for proteins in the HMGB1\/TLR4\/NF\u2010\u03baB pathway, TNF\u2010\u03b1 (via Western blot and immunofluorescence), and microglial activation (Iba\u20101 via immunofluorescence). The mRNA levels of these targets were assessed by qPCR at 7 and 28 days. Spinal cord tissue was evaluated for axonal integrity (NF200 via immunofluorescence) and for motor neuron survival (Nissl staining) at 28 days post\u2010injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EA treatment significantly improved locomotor and postural recovery compared to the SCI group. Concurrently, EA suppressed the SCI\u2010induced upregulation of HMGB1, TLR4, NF\u2010\u03baB, and TNF\u2010\u03b1 in the brain throughout the subacute (Day 7), transition (Day 14), and chronic (Day 28) phases, thereby inhibiting microglial activation. This neuroprotective effect was accompanied by spinal motor neuron survival and axonal integrity. The co\u2010administration of an HMGB1 inhibitor with EA established the pathway's necessity by showing that the resulting potentiation of therapeutic outcomes positions the HMGB1\/TLR4\/NF\u2010\u03baB axis as a central mechanism for EA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EA effectively ameliorates motor dysfunction following SCI by attenuating neuroinflammation in the frontal cortex. The underlying mechanism is causally linked to the downregulation of the HMGB1\/TLR4\/NF\u2010\u03baB signaling axis. The enhanced neuroprotection observed when combining EA with HMGB1 inhibition validates this signaling axis as the primary and essential target for EA's therapeutic effects in SCI management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71215","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:53:56Z","timestamp":1768888436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting the Spinal Cord\u2010Brain Axis: Electroacupuncture Mitigates Remote Frontal Cortex Neuroinflammation via HMGB1\/TLR4 to Aid Functional Recovery After Spinal Cord Injury"],"prefix":"10.1002","volume":"16","author":[{"given":"Yu","family":"Ning","sequence":"first","affiliation":[{"name":"School of Acupuncture, Moxibustion and Tuina Beijing University of Chinese Medicine  Beijing 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Acupuncture, Moxibustion and Tuina Beijing University of Chinese Medicine  Beijing China"},{"name":"Department of Rehabilitation The Third Affiliated Hospital of Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keduo","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Acupuncture, Moxibustion and Tuina Beijing University of Chinese Medicine  Beijing China"},{"name":"Department of Rehabilitation The Third Affiliated Hospital of Beijing University of Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Clinical Medicine Hainan Vocational College of Medicine  Haikou 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