Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for astronauts. Astrocytes are major cellular regulators of blood-brain barrier permeability that also modulate neuroinflammation and neuronal health. However, astrocyte roles in regulating CNS and blood-brain barrier responses to space radiation remain little understood. In this work, a high-throughput organ-on-a-chip system seeded with human iPSC-astrocytes and/or brain endothelial cells was used to evaluate blood-brain barrier impairments and astrocyte functions 1-7 days after exposure to 600 MeV/n 56Fe particles and simplified simulated galactic cosmic rays. It was shown that simulated deep space radiation causes vascular permeability, oxidative stress, inflammation and delayed astrocyte activation in a pattern resembling CNS responses to brain injury. Furthermore, the results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability acutely after irradiation, followed by switching to a more protective phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion during the subacute stage.
Overall, the human CNS model used in this study suggests astrocyte regulatory mechanisms as targets for countermeasures to mitigate human BBB impairments during deep space exploration. Furthermore, this method could be helpful for future space biology studies.
Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model
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