Glioblastoma-derived extracellular vesicles released after radiation promote cognitive impairment through...

Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Cognitive impairment is a common sequela in glioblastoma survivors, yet the underlying mechanisms remain poorly understood. Extracellular vesicles (EVs) derived from glioblastoma are established mediators of intercellular signaling within the tumor microenvironment. Here, we investigated whether GBM-derived EVs released after radiation treatment (RT-EVs) regulate cognitive function. Treatment with RT-EVs was associated with cognitive deficits and neuroinflammatory responses in vivo. In vitro, RT-EVs activated the NFκB pathway and induced the release of neurotoxic H ₂ O ₂ . Importantly, NFκB p50 knockdown abolished the H ₂ O ₂ release previously triggered by RT-EVs, demonstrating mechanistic dependence on NFκB signaling. Collectively, these findings identify GBM-derived RT-EVs as critical mediators of cognitive impairment through NFκB-dependent redox imbalance. EV-driven redox dysregulation may therefore represent a therapeutic target to mitigate GBM-associated cognitive dysfunction.

Radiation induces the release of glioblastoma-derived EVs that are biologically different from those released under non-irradiated conditions.EVs released from glioblastoma after radiation are sufficient to impair cognition EVs from irradiated glioblastoma can activate microglia via NFκB and induce production of neurotoxic H ₂ O ₂.