Synchrotron-Generated X-Ray Microbeam Irradiation Enhances Hippocampal Neurogenesis in Healthy Rats

Synchrotron-generated microbeam X-rays are emerging as a novel promising therapeutic strategy for the treatment of drug-resistant epilepsy. One important limiting factor of radiotherapy for the treatment of drug-resistant epilepsy, brain tumors and metastases is the onset of cognitive deficits and dementia due to the reduction of hippocampal neurogenesis. The long-term safety of synchrotron-generated X-ray microbeam irradiation is a concern for translating this novel irradiation technique to humans. Here we show the effects of synchrotron-generated X-ray microbeam irradiation of the dorsal hippocampus in healthy rats in the short-, mid- and long-term. Healthy rats were irradiated with either homogeneous broadbeams (10 Gy) or 2 arrays composed of 10 parallel microbeams each (75 μm wide, spaced 400 μm center-to-center, 300 or 600 Gy) in the cerebral cortex and the dorsal hippocampus. Rats underwent behavioral testing, histological and immunohistochemical analysis, and stereological counts of proliferating cells in the hippocampal dentate gyrus. X-ray microbeam irradiation delivering peak doses of 300 Gy reduced depressive-like behavior, and this antidepressant effect was associated with an increase of hippocampal dentate gyrus neurogenesis in the short-, mid- and long-term. Spontaneous locomotor activity, hippocampal-mediated cognition and microvessels were not affected by X-ray microbeam irradiation. These data shed light on the long-term radiobiology of microbeams in the central nervous system and lay the groundwork for their use in treating drug-resistant epilepsy and other neurological disorders associated with reduced neurogenesis.