Radiotherapy to the brain, often used to treat cancer, can lead to long-term problems with memory and thinking. One possible cause is inflammation in the brain, but how this develops over time is not well understood. In our preprint, we followed changes in the brain from a few hours up to one year after irradiation in an animal model. We found that key immune cells in the brain, called microglia, respond in a delayed and disrupted way: many are lost, fail to recover properly and are partly replaced by cells coming from outside the brain. These changes were also seen in human brain tissues, but we are underpowered for these samples (only n=1) and therefore need more cases to test our hypothesis that what we see in our animal model is directly observable in human cases. In addition, we identified two stages of disrupted brain activity—an early phase linked to inflammation and a later phase linked to abnormal connections between neurons. Together, these findings improve our understanding of how radiotherapy affects the brain and may help guide treatments to protect cognitive function in cancer survivors.