Electrophysiological and neuroimmune responses of a cortical tissue model to chronic gamma radiation exposure

Abstract Exposure to chronic space radiation is a major health concern for long-duration missions beyond low Earth orbit. While most experimental studies simulate mission-relevant doses using acute irradiation, astronauts will experience persistent low-dose-rate exposure over months. Here, we used engineered three-dimensional (3D) mouse cortical tissue models and two-dimensional (2D) primary cortical cultures to investigate the effects of radiation dose rate on neuroglial function, inflammatory responses, and neuronal network activity. Cultures were exposed to a cumulative 0.5 Gy dose of γ-radiation delivered either acutely (1 h) or chronically (166 h), with or without pretreatment using the radioprotective agent amifostine. In 3D cortical tissue models, we quantified DNA damage, astrocyte and microglia reactivity, neuronal survival, neurite morphology, and secretion of pro-inflammatory cytokines. In parallel, microelectrode array recordings were used to assess electrophysiological function in 2D neuronal networks following γ-radiation or treatment with the radiomimetic drug bleomycin. Acute gamma radiation induced modest astrocyte activation, whereas chronic exposure caused limited neuroimmune alterations. Neither exposure paradigm impaired neuronal network activity, despite measurable DNA damage responses. Together, these findings indicate that neuronal function is preserved following low-dose-rate gamma irradiation while glial populations display selective sensitivity to radiation exposure.