{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:55:16Z","timestamp":1787064916078,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal cord injury is a severe central nervous system disorder with high morbidity and mortality, whose pathological process is divided into primary and secondary injury. The regulation of neuroinflammation is a critical link in secondary injury, forming a positive feedback loop involving microglia and peripheral immune cells. Low\u2010intensity pulsed ultrasound, a noninvasive physical therapy, exhibits significant potential in regulating inflammation and promoting microangiogenesis in orthopedics and nerve repair, providing new insights for intervening in the secondary pathological cascade of SCI. However, its therapeutic effects and underlying molecular mechanisms in SCI treatment have not been systematically and in\u2010depth explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 88 Sprague\u2013Dawley rats were randomly divided into the sham operation group, SCI group, and SCI\u2009+\u2009LIPUS treatment group (nine subgroups with different parameter combinations) to establish a T10 segment SCI model. The SCI\u2009+\u2009LIPUS group received LIPUS intervention (20\u2009min\/day, 5\u2009days\/week) starting 1\u2009day after modeling. Basso, Beattie, and Bresnahan locomotor scores were used to evaluate hindlimb motor function at multiple time points postoperatively. On Day 28, spinal cord samples were collected for hematoxylin\u2013eosin staining and immunofluorescence staining to assess cavity area, microglial infiltration, and inflammatory microenvironment changes. In in\u00a0vitro experiments, a lipopolysaccharide\u2010induced BV2 microglial polarization model was established, followed by LIPUS intervention. Cell Counting Kit\u20108 assay, quantitative polymerase chain reaction, immunofluorescence staining, and Transwell co\u2010culture with HT22 neurons combined with Western blot were used to detect cell viability, inflammatory factor expression, and neuronal apoptosis. RNA sequencing and bioinformatics analysis (GO\/KEGG enrichment, protein\u2013protein interaction network construction) were conducted on spinal cord tissues from the SCI and SCI\u2009+\u2009LIPUS groups to screen differentially expressed genes and hub genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BBB scores showed that the SCI\u2009+\u2009LIPUS group (especially with the parameters of 180\u2009mW\/cm\n                      <jats:sup>2<\/jats:sup>\n                      and 1.5\u2009MHz) exhibited significantly better hindlimb motor function than the SCI group from day 7 postoperatively, persisting until day 28 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). HE and immunofluorescence staining indicated that LIPUS reduced spinal cord cavity area, inhibited microglial activation, promoted M2\u2010type microglial polarization, and alleviated secondary inflammation. In\u00a0vitro experiments confirmed that LIPUS enhanced BV2 cell viability and proliferation, upregulated the expression of anti\u2010inflammatory factors (IL\u201010, Arg\u20101), downregulated pro\u2010inflammatory factors (IL\u20106, TNF\u2010\u03b1), and suppressed HT22 neuron apoptosis by inhibiting inflammatory factor secretion from BV2 cells. RNA sequencing identified 67 DEGs (26 upregulated, 41 downregulated) between the SCI\u2009+\u2009LIPUS and SCI groups, enriched in immune defense, extracellular matrix remodeling, NOD\u2010like receptor, and IL\u201017 signaling pathways. Hub genes including CXCR2 were identified, and CXCR2 downregulation was confirmed to be involved in LIPUS\u2010mediated anti\u2010inflammatory effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LIPUS effectively alleviates neuroinflammation after SCI and promotes neurological function recovery by regulating microglia\u2010mediated neuroinflammation, whose mechanism is associated with the modulation of NOD\u2010like receptor, IL\u201017 signaling pathways and the downregulation of hub genes such as CXCR2. This study provides a scientific basis for the clinical application of LIPUS in SCI treatment and a theoretical foundation for exploring multi\u2010modal therapeutic strategies combining LIPUS with other therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70849","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:06:09Z","timestamp":1774688769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Low\u2010Intensity Pulsed Ultrasound Promotes Spinal Cord Injury Recovery by Regulating Microglia\u2010Mediated Neuroinflammation"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiaoyu","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics Shanghai Changhai Hospital  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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