Drug intervention of radiation exposure induced BBB injury via mitochondria-mediated non-infectious inflammation

Radiation-induced brain injury (RIBI) is a series of brain injuries caused by exposure to high doses of ionizing radiation, characterized by severe cognitive dysfunctions and brain necrosis.In this study, we described a biomimetic human blood-brain barrier (BBB) model that allowed to probe the responses to radiation exposure.This RNA-seq data illustrated that representative RIBI-associated pathological responses including BBB compromise, DNA break, inhibited cell proliferation, cell swelling and release of pro-inflammatory cytokines following acute radiation exposure. Based on the pathogenic mechanism study, we carried out drug screening and identified two drugs effectively ameliorated radiation-induced inflammation and BBB injury on the BBB model. Collectively, the study uncovered an unknown mitochondria-mediated inflammation involved in the pathogenesis of RIBI, indicating mitochondria can be utilized as a potential target for developing new radioprotective measures. Overall design: In this study, we developed a biomimetic human blood-brain barrier (BBB) model composed of multiple cellular components to evaluate the therapeutic effect of radiation-induced brain injury (RIBI) following exposure to ?-ray by drug intervention. The controls are from blood channel (n=3) that receive no radiation exposure and are compared to blood channel (n=3), a JAK1 inhibitor Intervention (n=3) and a mitochondrial protectant Intervention (n=3) that receive 16Gy of radiation, respectively.