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However, the pathogenesis of RIBI is not fully understood, and no effective intervention is available. This work describes a blood\u2013brain barrier (BBB) microphysiological system (MPS), that allowed to explore the responses of BBB and distinct brain cells to radiation exposure. Following acute exposure to radiation of X\u2010ray or \u03b3\u2010ray, characteristic RIBI\u2010associated pathological responses are observed, including BBB compromise, DNA breaks, inhibited cell proliferation, cell hypertrophy, and proinflammatory cytokine release. Among the distinctive types of cells, brain endothelial cells show the highest radiosensitivity as compared to other cells in the MPS. Intriguingly, X\u2010ray and \u03b3\u2010ray radiation consistently induce prominent sterile inflammation responses, especially type I interferon response, in the BBB MPS. These responses are mediated by radiation\u2010induced mitochondrial DNA release and subsequent activation of cGAS\u2010STING signaling pathway. Furthermore, it is found abrocitinib (JAK1 inhibitor) and idebenone (mitochondrial protectant) can attenuate radiation\u2010induced inflammation and ameliorate injuries in the BBB MPS. These findings reveal the involvement of mitochondria\u2010mediated sterile inflammation in RIBI pathogenesis, identifying mitochondria as a potential target for new radioprotective measures.<\/jats:p>","DOI":"10.1002\/advs.202502356","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T05:54:34Z","timestamp":1748411674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Radiation Exposure Induced Blood\u2013Brain Barrier Injury via Mitochondria\u2010Mediated Sterile Inflammation"],"prefix":"10.1002","volume":"12","author":[{"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui 230026 P. R. China"},{"name":"Suzhou Institute for Advanced Research University of Science and Technology of China  Suzhou 215123 P. R. 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