{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:12Z","timestamp":1790794512624,"version":"4.1.0"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"869","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82322023"],"award-info":[{"award-number":["82322023"]}],"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":["82371398"],"award-info":[{"award-number":["82371398"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology of the People\u00b4s Republic of China","award":["2023YFC2306502"],"award-info":[{"award-number":["2023YFC2306502"]}],"id":[{"id":"https:\/\/ror.org\/027s68j25","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Opening Foundation of State Key Laboratory of Neurology and Oncology Drug Development","award":["SKLSIM-20250095"],"award-info":[{"award-number":["SKLSIM-20250095"]}]},{"name":"Neuro- Microscopy and Minimally Invasive Translational Medicine Innovation Center","award":["CXZX202212"],"award-info":[{"award-number":["CXZX202212"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,9,30]]},"abstract":"<jats:p>Patients with chronic traumatic brain injury (cTBI) experience long-term exacerbated neurological decline, which is even more severe in older patients, yet the underlying mechanisms remain unclear. Cranial bone marrow (CBM) has recently been recognized as an adjacent immune surveillance organ of the brain that rapidly responds to acute brain injury. We investigated whether CBM-derived immune cells contribute to chronic neuroinflammation after cTBI by integrating clinical specimens, cell-tracing strategies, multiomics profiling, transgenic animal assays, adoptive cell transfer, and a proof-of-concept randomized clinical trial. We found that cTBI induced persistent aberrant myelopoiesis in the CBM, characterized by expansion of inflammatory monocytes\/macrophages (Mo\/Macs), which aggravated with aging. These CBM-derived Mo\/Macs actively migrated into brain parenchyma, where they fueled chronic neuroinflammation and drove neurological deficits. Mechanistically, age-related peroxisome proliferator\u2013activated receptor \u03b1 (PPAR\u03b1) deficiency caused lipid metabolism dysfunction in these Mo\/Macs, enhancing H3K4me3-mediated regulation of inflammatory chromatin states and thereby promoting neuroinflammation. Activation of PPAR\u03b1 via fenofibrate rectified Mo\/Mac lipid metabolism and reduced inflammatory Mo\/Mac infiltration into the brain. In a proof-of-concept randomized clinical trial enrolling 40 older adult patients with cTBI, fenofibrate treatment reduced plasma neurofilament light chain levels and improved cognitive functions. Together, these findings demonstrate that CBM-originated inflammatory Mo\/Macs may serve as key inflammatory drivers of cTBI and further show that fenofibrate represents a potential therapeutic strategy for cTBI treatment in older adults.<\/jats:p>","DOI":"10.1126\/scitranslmed.aef5898","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:33Z","timestamp":1790791113000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Cranial bone marrow\u2013derived monocytes promote neuroinflammation in chronic traumatic brain injury"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4755-5444","authenticated-orcid":true,"given":"Zhichao","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu 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