Staying longer in outer space will inevitably increase the health risks of astronauts due to the exposures to galactic cosmic rays and solar particle events. Exposure may pose a significant hazard to space flight crews not only during the mission but also later, when slow-developing adverse effects could finally become apparent. The body of literature examining ground-based outcomes in response to high-energy charged-particle radiation suggests differential effects in response to different particles and energies. Numerous animal and cellular models have repeatedly demonstrated the negative effects of high-energy charged-particle on the brain and cognitive function. However, research on the role of space radiation in potentiating cardiovascular dysfunction is still in its early stages. This review summarizes the available data from studies using ground-based animal models to evaluate the response of the brain and heart to the high-energy charged particles of GCR and SPE, addresses potential sex differences in these effects, and aims to highlight gaps in the current literature for future study.