Risks of cognitive detriments after low dose heavy ion and proton exposures.

Purpose: Heavy ion and proton brain irradiations occur during space travel and in Hadron therapy for cancer. Heavy ions produce distinct patterns of energy deposition in neuron cells and brain tissues compared to X-rays leading to large uncertainties in risk estimates. We make a critical review of findings from research studies over the last 25 years for understanding risks at low dose. Conclusions: A large number of mouse and rat cognitive testing measures have been reported for a variety of particle species and energies for acute doses. However, tissue reactions occur above dose thresholds and very few studies were performed at the heavy ion doses to be encountered on space missions (<0.04 Gy/y) or considered dose-rate effects, such that threshold doses are not known in rodent models. Investigations of possible mechanisms for cognitive changes have been limited by experimental design with largely group specific and not subject specific findings reported. Persistent oxidative stress and activated microglia cells are common mechanisms studied, while impairment of neurogenesis, detriments in neuron morphology, and changes to gene and protein expression were each found to be important in specific studies. Future research should focus on estimating threshold doses carried out with experimental designs aimed at understating causative mechanisms, which will be essential for extrapolating rodent findings to humans and chronic radiation scenarios, while establishing if mitigation are needed.