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Updated: May 26, 2026

Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
Published on: November 14, 2013
Six-month evaluation of normal mouse brain side effects: Comparing FLASH and conventional proton partial brain
Manuel Bernabei1,2,3, Sindi Nexhipi1,4, Elisabeth Bodenstein1,3
1OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
Background And Purpose:
Preclinical studies demonstrated ultra-high dose-rate radiation treatment ability to effectively control local tumour growth while reducing damage to healthy tissues. This methodological pilot study was designed and conducted to establish an irradiation setup and to generate data for future studies investigating long-term side effects of mouse brain irradiation with proton FLASH (FLASH-PT) and conventional proton therapy (CONV-PT).
Material And Methods:
Fourteen C57BL/6JRj female mice were partial brain irradiated with a single dose of 22.5 Gy using a proton spread-out Bragg peak (SOBP). Mice were randomised into FLASH-PT (268 Gy/s, n = 6), CONV-PT (0.27 Gy/s, n = 6), and unirradiated sham groups (n = 2). In addition to skin reaction monitoring as short-term endpoint, regular contrast-enhanced magnetic resonance imaging (MRI) was performed during the six-month follow-up. Brains were formalin-fixed and paraffin-embedded and stained to assess activation of microglia.
Results:
The analysis of skin reactions demonstrates a trend in tissue-sparing effect for the FLASH group. In the brain MRI, no contrast enhancement was observed after irradiation. Although no group-level differences in microglia activation were observed between FLASH-PT and CONV-PT, both treatments showed increased density of activated microglia, which was distinct in specific regions within the periventricular area.
Conclusion:
The established irradiation setup allowed for a clinically relevant approach to preclinical FLASH-PT research. Partially irradiated brain showed no microglia-related FLASH effect. Further studies are required to fully comprehend dose-effect curves and timing for the FLASH effect in the brain.
