Session Item

Proton therapy is increasingly being used as an alternative to conventional photon-based radiotherapy to reduce normal tissue radiation dose and side effects in the treatment of brain tumors. Due to their physical properties, protons allow the potential sparing of brain regions that contribute the most to the development of neurocognitive dysfunction. However, current knowledge on regional responses is largely limited to the hippocampus. This study aims to identify which brain regions are most vulnerable to radiation and might increase the risk of neurocognitive dysfunction.

High-precision brain irradiation with 14 Gy protons (150 MeV) was delivered to 100%, 50% anterior and 50% posterior sub-volumes of the rat brain. Cognitive function was measured at different time points using the Novel Object Recognition test, the Barnes maze test and the Rotarod test. Additionally, the effects of partial brain proton irradiation on the innate neuro-inflammatory response were analyzed by semi-automatically extracting microglial morphological parameters from different regions of the rat brain.

Irradiation of the 50% anterior brain sub-volume leads to a greater loss in memory function and learning than irradiation of the 50% posterior brain sub-volume, as measured by the Novel Object Recognition and Barnes maze tests. Although this difference was evident at 12 weeks after irradiation, it largely resolved at 48 weeks after irradiation. Rotarod performance was similarly impaired in all treatment groups at 12 weeks after irradiation. However, at 48 weeks after irradiation, the 50% anterior irradiated animals showed a significant improvement, while performance in the other groups declined further. Along with the differential cognitive response, we analyzed in-field and out-of-field inflammatory responses. Preliminary principal component analysis identified 6 different morphology-based microglial cell clusters in the cortex and inferior colliculus. These regions showed increased microglial activation depending on whether they were included in the radiation field.

Our data indicate that irradiation of the 50% anterior brain sub-volume leads to a greater decline in memory and spatial learning. In contrast, the 50% posterior brain sub-volume seems to be more important for locomotor function, skill and speed learning. Overall, these data suggest a regional variation in loss of neurocognitive function between the anterior and posterior parts of the brain, which might be partly mediated by region-specific microglial cell activation.