HIGH-ENERGY (HZE) RADIATION EXPOSURE CAUSES DELAYED AXONAL DEGENERATION AND ASTROGLIOSIS IN THE CENTRAL NERVOUS SYSTEM OF RATS

Limiting the biological effects of cosmic radiation will be a key factor in determining the success of long duration space missions. The purpose of this study is to determine if exposure to high-energy radiation (HZE) leads to central nervous system (CNS) injury and astrogliosis. Astrogliosis, the ubiquitous response of astrocytes to CNS injury, can prevent regeneration and neurite outgrowth due to the formation of a glial scar. Ionizing radiation is known to be a potent stimulus of CNS injury and results in the activation of astrocytes accompanied by neuronal degeneration. It is unknown at this time if similar processes occur in the CNS following HZE exposure. Animals received whole-body irradiation with a 600 MeV/nucleon 56Fe beam in a single fraction of 0 or 4 Gy. Rats were euthanized at 1, 6, and 12 months post-exposure and brain tissue was stored for histological analysis. Antibodies directed against glial fibrillary acidic protein (GFAP) were used to characterize the astrocytic response. A modified Gallyas silver stain was performed to identify neuronal and axonal degeneration. When compared to controls, irradiated rats showed evidence of axonal degeneration in white matter with coinciding gliosis. The axonal degeneration was more pronounced at 12 months (882 degenerating axons per whole-brain section, 16 for controls) compared to 1 month post-exposure (120 degenerating axons per whole-brain section, 0 for controls), suggesting a delayed injury mechanism. GFAP immunohistochemistry demonstrated astrogliosis in the form of hypertrophy of astroglial process within the regions of axonal degeneration. Astrogliosis was also more evident at 12 months compared to 1 month post-exposure. These observations demonstrate that exposure to HZE radiation is a potent stimulator of CNS injury and astrogliosis and suggest a delayed and sustained mechanism. (Supported by NASA Grant #NNJO4HD80G to AO)