Travel beyond Earth's atmosphere and magnetosphere and exposure to microgravity can harm human health, and understanding these effects is essential for successful crewed spaceflight. Potential impacts on the central nervous system (CNS) are particularly important. Ground-based cellular and animal research will help quantify CNS risk from space radiation on long-duration missions and support development of optimized countermeasures. Acute and late CNS risks from galactic cosmic rays (GCRs) and solar proton events (SPEs) are a documented concern for human exploration. Historically, CNS effects in adults exposed to low-to-moderate doses of ionizing radiation (0–2 Gy; 1 Gy = 100 rad) were not a major focus, but the heavy-ion component of space radiation poses distinct biophysical challenges compared with terrestrial radiation. Soon after cosmic rays were discovered, concern about CNS effects arose with the prediction that single high-charge, high-energy (HZE) nuclei traversing the retina would produce light flashes—a phenomenon confirmed by Apollo astronauts in 1970 and 1973. HZE nuclei can create a column of severely damaged cells, or a microlesion, along their path through tissue, raising concern about serious impacts on the CNS. In recent years, concerns have arisen about neurogenesis and its impairment by HZE nuclei observed in experimental CNS models. Human epidemiology informs risk estimates for cancer, acute radiation effects, and cataracts, but it is not viable for estimating CNS risks from space radiation. At doses above a few gray, patients treated with radiation (e.g., gamma rays and protons) for cancer experience detrimental CNS changes; typical treatment doses are about 50 Gy, well above exposures expected in space even during a large solar particle event. Thus, of the four categories of space radiation risks—cancer, CNS, degenerative, and acute radiation syndromes—the CNS risk depends most heavily on animal experimental data. Understanding and mitigating CNS risks requires a vigorous research program drawing on cellular and animal models and on methods to extrapolate risks and evaluate potential countermeasures for astronauts. Several studies using heavy-ion beams that simulate space radiation provide evidence of CNS effects: exposure to HZE nuclei at low doses (<50 cGy) significantly induces neurocognitive deficits in mice and rats, including learning and behavioral changes and altered operant responses. Exposures to equal or higher doses of low-LET radiation (e.g., gamma or X-rays) do not produce similar effects. The threshold for performance deficits following HZE exposure depends on particle characteristics, such as linear energy transfer (LET), and the animal’s age at exposure. Performance deficits have been observed at doses comparable to those expected on a Mars mission (<0.5 Gy). Neurocognitive deficits affecting the dopaminergic system resemble aging and appear unique to space radiation. HZE exposure also disrupts neurogenesis in mice at low doses (<1 Gy), causing a dose-related reduction in new neurons and oligodendrocytes in the subgranular zone (SGZ) of the hippocampal dentate gyrus. Exposure to HZE nuclei and protons at low doses induces reactive oxygen species (ROS) in neuronal precursor cells that can persist for months; antioxidants and anti-inflammatory agents may mitigate these effects. HZE and proton exposure also elicit neuroinflammation, and age-related genetic changes increase CNS radiosensitivity. Animal studies using HZE irradiation show significant CNS changes at dose levels relevant to NASA, but the implications for astronaut morbidity remain unclear. One model of late tissue effects suggests that significant effects occur at lower doses but with increased latency. Studies to date have used relatively small numbers of animals (fewer than 10 per dose group), so testing of dose-threshold effects at lower doses (less than 0.5 Gy) has been insufficient. Extrapolating animal data to humans is a major challenge and may be limited by small animal study sizes. The role of dose protraction has not been studied. No reliable method exists to extrapolate existing observations to possible cognitive changes, performance degradation, or late central nervous system (CNS) effects in astronauts.

New systems-biology approaches offer promising tools to address this challenge. Recently, eight gaps were identified in projecting CNS risks; research on new risk-assessment approaches is needed to provide the data and knowledge required to develop CNS risk-projection models for space radiation.

Both galactic cosmic rays (GCRs) and solar particle events (SPEs) are of concern for CNS risks. Major GCR components include protons, α-particles, and high charge and energy (HZE) nuclei, with a broad energy spectrum ranging from a few tens to more than 10,000 MeV per nucleon (MeV/u). In interplanetary space, galactic cosmic rays (GCRs) are expected to deliver an organ absorbed dose of more than 0.2 Gy per year and a dose equivalent exceeding 0.6 Sv per year. The high energies of GCRs allow them to penetrate hundreds of centimeters of most materials, making shielding an impractical mitigation for GCR risks to the central nervous system. Solar particle events (SPEs) can produce absorbed doses above 1 Gy for crew in thinly shielded spacecraft or during extravehicular activity. Although SPE particle energies (tens to hundreds of MeV) can be attenuated by shielding, protecting against the largest events would be costly.