Abstract
Traditionally, the brain has been regarded as a relatively insensitive late-reacting tissue, with radiologically detectable damage not being reported at doses < 60 Gy. When NASA proposed interplanetary exploration missions, it was required to conduct an intensive health and safety evaluation of cancer, cardiovascular, and cognitive risks associated with exposure to deep space radiation (SR). The SR dose that astronauts on a mission to Mars are predicted to receive is ~300 mGy. Even after correcting for the higher RBE of the SR particles, the biologically effective SR dose (<1 Gy) would still be 60-fold lower than the threshold dose for clinically detectable neurological damage. Unexpectedly, the NASA-funded research program has consistently reported that low (<250 mGy) doses of SR induce deficits in multiple cognitive functions. This review will discuss these findings and the radical paradigm shifts in radiobiological principles for the brain that were required in light of these findings. These included a shift from cell killing to loss of function models, an expansion of the critical brain regions for radiation-induced cognitive impediments, and the concept that the neuron may not be the sole critical target for neurocognitive impairment. The accrued information on how SR exposure impacts neurocognitive performance may provide new opportunities to reduce neurocognitive impairment in brain cancer patients.