Effects of whole brain proton irradiation at conventional or ultra-high dose rate (FLASH), in adult male Sprague Dawley rats

Radiation is an effective treatment for many brain tumors, but often causes cognitive impairment. Ultra-high dose rate (FLASH) radiotherapy is less toxic to many normal tissues and may protect against adverse cognitive effects of cranial irradiation. Adult male Sprague Dawley rats received a single 18 Gy fraction of cranial irradiation with protons at 1 Gy/s (CV), 60 Gy/s (FLASH-60), 95 Gy/s (FLASH-95), or sham treatment (Control) (n ≥ 22/group). Rats were tested in open-field, acoustic (ASR) and tactile startle (TSR), novelty preference, radial water maze (RWM), Morris water maze (MWM), Cincinnati water maze configurations A and B (CWM-A CWM-B), and novelty tests. Locomotion was decreased and TSR increased in all irradiated rats and ASR increased in FLASH-95 rats compared with Controls. In MWM acquisition and reversal, the CV and FLASH-60 rats had reduced path efficiency but during shift and shift reversal all irradiated rats had increased latencies and reduced path efficiencies compared with Controls. In CWM-A all irradiated rats performed below Controls. There were no differences found in CWM-B, novelty tests, or RWM. In summary, FLASH treatment after 18 Gy cranial proton irradiation did not result in reduced cognitive toxicity.