Ionizing radiation acutely stimulates iron accumulation in the olfactory bulb

Radiation therapy leads to structural and functional changes in the brain resulting in a time-dependent cognitive decline. There are limited options to ameliorate this side-effect of therapy that significantly impacts patient quality of life; thus, a more robust understanding of the radiation injury pathogenesis is required. A commonly reported acute effect of cranial irradiation is the disruption of olfactory function, an effect that is also commonly seen in a variety of neurodegenerative processes ( e.g., Parkinson’s Disease). Iron accumulation has been demonstrated in neurodegenerative processes and can acutely affect olfactory function; thus, we hypothesized that cranial irradiation induces acute iron accumulation in the olfactory bulb of mice. Following 12 Gy of whole brain irradiation, a significant acute increase in iron was observed in the olfactory bulb as compared to the rest of the brain which corresponds with decreased olfactory function. Moreover, the use of T2* MRI as a surrogate marker of iron accumulation revealed significant loss in T2* signal in the glomerular cell layer of the olfactory bulb that corresponded with subsequent volume loss. These results suggest that the olfactory bulb is particularly sensitive to ionizing radiation induced iron accumulation with the glomerular cell layer being a potential key vulnerability.