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Extracellular vesicles (EVs) such as exosomes, microvesicles (MVs) and apoptotic bodies (ApoBDs) serve as critical vehicles mediating intercellular communication in the central nervous system (CNS) following TBI. The biogenesis and the content of EVs, including proteins, lipids and RNAs, are greatly changed and involved in the evolution of inflammation or tissue repairing after TBI. In this overview, we recapitulate the cellular origin of EVs and the function of EVs in the neuroinflammatory process after TBI, highlighting the dual regulatory roles of EVs in the biological response to TBI, whereby certain EV populations amplify secondary injury cascades, while others promote endogenous repair and recovery processes. We next investigate the progress in EV engineering and targeted delivery systems and report the potential mechanisms, emphasize the prospects and potential of engineered EVs for therapy, and comment on challenges and perspectives for clinical application in TBI.<\/jats:p>","DOI":"10.3390\/ijms27125322","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:49:51Z","timestamp":1781257791000},"page":"5322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Dual Roles of Extracellular Vesicle Subtypes in Regulating Traumatic Brain Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Xu","family":"Zhang","sequence":"first","affiliation":[{"name":"Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Xu","sequence":"additional","affiliation":[{"name":"Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing 210008, China"},{"name":"Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/S1474-4422(22)00309-X","article-title":"Traumatic Brain Injury: Progress and Challenges in Prevention, Clinical Care, and Research","volume":"21","author":"Maas","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol. 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