Mechanisms of radiation-induced brain damage: from neurodevelopment to systemic crosstalk
Mechanisms of radiation-induced brain damage: from neurodevelopment to systemic crosstalk
Radiotherapy is an important treatment for brain tumors, but it can also harm nearby healthy brain tissue. This damage may lead to long-term problems with memory and attention, which can significantly impact a patient’s quality of life. Currently, there are no effective treatments to prevent these side effects.
This thesis of Yuting Jiang investigates the impact of irradiation on both the adult and developing brain, using pre-clinical animal models and lab-grown human brain organoids that mimic early brain development. We focused on microglia, the brain’s immune cells that help maintain brain health. We found that conventional photon radiation causes microglia to enter a persistent “primed” state, making them more sensitive and reactive to future immune challenges. Proton therapy, a modern radiotherapy technique often used in pediatric cancer patients, can more precisely target tumors while sparing healthy tissues. We observed that proton therapy induces a localized microglial priming response. The extent of priming caused by the proton plateau region, which mainly affects healthy tissue, was similar to that seen with photon irradiation.
However, in the proton spread-out Bragg peak (SOBP) region, which covers the tumor and a small amount of surrounding tissue, a stronger microglial priming response was observed. In the human brain organoid model, photon and proton plateau radiation induced similar gene expression profiles, while proton SOBP uniquely reduced synapse-related gene expression and disrupted neuronal communication. Beyond the brain, we also found that brain irradiation can affect the liver by increasing cell proliferation and enzyme activity.