Evaluating metabolic disruption following radiotherapy in the developing brain: a preclinical juvenile model

Motivation: Cognitive performance in paediatrics is severely impacted by current brain tumour treatment plans such as radiotherapy. Goal(s): Our goal is to decipher the underlying mechanism of this cognitive decline, which remains unknown and is particularly difficult to decipher in paediatric patients due to confounding developmental variables. Approach: Longitudinal 1H MRS analysis in the brain following radiotherapy in a juvenile rat model provides valuable insight into metabolic disruption. Results: Myo-inositol levels, linked to other neurodegenerative and cognitive conditions, were elevated in the hippocampus and cerebellum. Deviance in N-acetyl-aspartate levels between irradiated and healthy rats over a developmental period of 12.5 weeks was also revealed. Impact: 1H MR spectroscopy reveals valuable insight into longitudinal impacts of radiotherapy on the developing brain. A juvenile rat model enables acute and chronic alterations in inflammatory markers, membrane synthesis, bioenergetics and viability to be monitored, distinguishing irradiation and development effects.