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Updated: Jul 1, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Proton therapy induces a local microglial neuroimmune response
Daniëlle C Voshart1, Myrthe Klaver1, Yuting Jiang1
1Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 RB, The Netherlands; Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, Groningen 9700 AD, The Netherlands.
Background And Purpose:
Although proton therapy is increasingly being used in the treatment of paediatric and adult brain tumours, there are still uncertainties surrounding the biological effect of protons on the normal brain. Microglia, the brain-resident macrophages, have been shown to play a role in the development of radiation-induced neurotoxicity. However, their molecular and hence functional response to proton irradiation remains unknown. This study investigates the effect of protons on microglia by comparing the effect of photons and protons as well as the influence of age and different irradiated volumes.
Materials And Methods:
Rats were irradiated with 14 Gy to the whole brain with photons (X-rays), plateau protons, spread-out Bragg peak (SOBP) protons or to 50 % anterior, or 50 % posterior brain sub-volumes with plateau protons. RNA sequencing, validation of microglial priming gene expression using qPCR and high-content imaging analysis of microglial morphology were performed in the cortex at 12 weeks post irradiation.
Results:
Photons and plateau protons induced a shared transcriptomic response associated with neuroinflammation. This response was associated with a similar microglial priming gene expression signature and distribution of microglial morphologies. Expression of the priming gene signature was less pronounced in juvenile rats compared to adults and slightly increased in rats irradiated with SOBP protons. High-precision partial brain irradiation with protons induced a local microglial priming response and morphological changes.
Conclusion:
Overall, our data indicate that the brain responds in a similar manner to photons and plateau protons with a shared local upregulation of microglial priming-associated genes, potentially enhancing the immune response to subsequent inflammatory challenges.
Insights
Proton and photon radiation affect brain microglia similarly, causing neuroinflammation. This study clarifies proton therapy
Area of Science:
- Neuroscience
- Radiation Oncology
- Immunology
Background:
- Proton therapy is gaining traction for brain tumors, but its effects on normal brain tissue, particularly microglia, are not fully understood.
- Microglia, the brain's immune cells, are implicated in radiation-induced neurotoxicity.
- The molecular response of microglia to proton irradiation remains largely unknown.
Purpose of the Study:
- To investigate the molecular and functional response of microglia to proton irradiation.
- To compare the effects of protons versus photons on microglia.
- To assess the influence of age and irradiated brain volume on microglial response.
Main Methods:
- Rats were whole-brain irradiated with photons (X-rays), plateau protons, or spread-out Bragg peak (SOBP) protons, or received partial brain irradiation with plateau protons.
- RNA sequencing, qPCR, and high-content imaging were used to analyze microglial gene expression and morphology 12 weeks post-irradiation.
Main Results:
- Both photons and plateau protons induced similar transcriptomic changes related to neuroinflammation and microglial priming.
- Microglial priming was less pronounced in juvenile rats compared to adults.
- Spread-out Bragg peak protons showed a slightly increased priming response, while partial brain proton irradiation induced a localized microglial response.
Conclusions:
- The brain exhibits a comparable response to photons and plateau protons, characterized by localized upregulation of microglial priming genes.
- This microglial priming may enhance the brain's immune response to future inflammatory stimuli.
- Findings contribute to understanding the biological effects of proton therapy on the brain.
