{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:16:50Z","timestamp":1788448610577,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for Promotion of Science (JSPS) KAKENHI","award":["20K17930"],"award-info":[{"award-number":["20K17930"]}]},{"name":"Japan Society for Promotion of Science (JSPS) KAKENHI","award":["19H03408"],"award-info":[{"award-number":["19H03408"]}]},{"name":"Japan Society for Promotion of Science (JSPS) KAKENHI","award":["32300729"],"award-info":[{"award-number":["32300729"]}]},{"name":"National Natural Science Foundation of China","award":["20K17930"],"award-info":[{"award-number":["20K17930"]}]},{"name":"National Natural Science Foundation of China","award":["19H03408"],"award-info":[{"award-number":["19H03408"]}]},{"name":"National Natural Science Foundation of China","award":["32300729"],"award-info":[{"award-number":["32300729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1\u03b2), tumor necrosis factor-alpha (TNF-\u03b1), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components\u2014thrombin, heme, and ferrous ion\u2014 prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before\/after surgery.<\/jats:p>","DOI":"10.3390\/ijms25115889","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T13:32:55Z","timestamp":1716903175000},"page":"5889","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury"],"prefix":"10.3390","volume":"25","author":[{"given":"Shangze","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"},{"name":"School of Pharmaceutical Sciences, Tsinghua University, Beijing 100082, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-494X","authenticated-orcid":false,"given":"Dengli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Tomono","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4934-056X","authenticated-orcid":false,"given":"Li","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-9049","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-5005","authenticated-orcid":false,"given":"Yohei","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"},{"name":"Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, Okayama 7010193, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Yata","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nishibori","sequence":"additional","affiliation":[{"name":"Department of Translational Research & Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aromatario, M., Torsello, A., D\u2019errico, S., Bertozzi, G., Sessa, F., Cipolloni, L., and Baldari, B. 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