{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:50:31Z","timestamp":1782190231383,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Severe burns are known to provoke neuroinflammation and contribute to cognitive deficits, but the mechanism of action remains poorly understood. We hypothesize that early release of extracellular high mobility group box 1 (HMGB1), a key driver for inflammation, triggers the burn\u2212induced hyperinflammation and associated synaptic dysfunction. Unavoidable immobilization prolongs inflammation and worsens burn outcomes. We examined the therapeutic potential of an anti\u2212HMGB1 neutralizing antibody in improving the neurological outcomes in burned and immobilized rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adult male rats received &amp;gt;30% total body surface area (TBSA) scald burns. After injury, animals received either no treatment, chicken anti\u2212HMGB1, or isotype control IgY antibody (2 mg\/kg, intraperitoneal or combined with subcutaneous Alzet pump delivery). Burn\u2212injured, treated rats underwent 14 days of hindlimb unloading (HLU) in metabolic cages, followed by 7 days of mobile recovery. Burned rats without treatment were pair\u2212fed and housed in standard cages without suspension, as were sham\u2212burn controls. All animals were euthanized 21 days post\u2212injury for sample collection. Hippocampal synaptic integrity was evaluated using field electrophysiological recordings at Schaffer collateral synapses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Burn wound size was significantly increased in rats subjected to hindlimb unloading, accompanied by elevated IL\u221210 and IL\u22121\u03b2 levels. These alterations were mitigated by anti\u2212HMGB1 antibody treatment. Furthermore, anti\u2212HMGB1 administration moderated the activated CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and NK cells response. Electrophysiological analysis of hippocampal slices showed that burn\u2212HLU rats treated with vehicle, exhibited pronounced postsynaptic hyperexcitability and left\u2212shifted presynaptic excitability curves, consistent with synaptic dysfunction. These animals also demonstrated disrupted slope profiles and loss of basal-excitatory resolution, indicating heightened excitability and increased vulnerability to degeneration. Anti\u2212HMGB1 antibody treatment restored normal potentiation patterns and preserved both pre\u2212 and postsynaptic function in burned rats with 14-days hindlimb unloading.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Prolonged immobilization provoked pre\u2212 and post-synaptic hyperexcitability at Schaffer collateral synapses and exacerbated burn\u2212induced brain impairment in rats. Early reduction of systemic HMGB1 activity protected against inflammation, preserved the hippocampal synaptic plasticity, and restored long\u2212term potentiation and hippocampal integrity following burn injury and hindlimb unloading in rats.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1867953","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T04:32:38Z","timestamp":1782189158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immediate post-injury HMGB1 neutralization prevents synaptic dysfunction in burn and hindlimb unloaded rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Sravan Gopalkrishna Shetty","family":"Sreenivasa Murthy","sequence":"first","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, The University of Texas Medical Branch at Galveston","place":["TX, United States"]},{"name":"Department of Neurology, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"T\u00f6r\u0151","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Wyrick","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amina","family":"El Ayadi","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha J.","family":"Garg","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Mitchell Center for Neurodegenerative Disease, The University of Texas Medical Branch at Galveston","place":["TX, United States"]},{"name":"Department of Neurology, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juquan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Surgery, The University of Texas Medical Branch at Galveston","place":["TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2011.06.005","article-title":"Epidemiology of burns throughout the world. 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