Cardiovascular and central nervous system risk in astronauts: the minipig as a physiologically relevant radiation model

Humans will return to the Moon and travel to deep space on their journey to Mars. Space exploration presents significant hazards to human health, including exposure to ionizing radiation (IR) from galactic cosmic rays (GCR) and solar particle events (SPEs). Space radiation-induced carcinogenesis is considered a primary risk to astronaut health. However, cardiovascular disease (CVD) and central nervous system (CNS) dysfunction have emerged as significant health risks for astronauts. Small animal models, particularly rodents, have provided valuable information regarding IR effects on the cardiovascular and CNSs; however, these small animal models have limitations in mimicking human metabolism and physiology, highlighting the need for alternative models. Minipigs are highly translational cardiovascular and neurovascular models due to their close similarities to humans in anatomy, physiology, metabolism, and immune responses. Their use enables clinically relevant assessment of space radiation-induced cardiovascular and neurological effects. This review highlights the advantages and limitations of minipigs as radiation models, including their utility for investigating sex-specific responses and their integration with emerging microphysiological systems. Together, these approaches provide a translational platform for mechanistic discovery, biomarker identification, risk assessment, and the development of countermeasures to protect astronaut health during future deep-space missions.