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Updated: Jul 3, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Radiotherapy induces persistent innate immune reprogramming of microglia into a primed state
Daniëlle C Voshart1, Takuya Oshima2, Yuting Jiang1
1Department of Biomedical Sciences, Section of Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Abstract:
Over half of patients with brain tumors experience debilitating and often progressive cognitive decline after radiotherapy treatment. Microglia, the resident macrophages in the brain, have been implicated in this decline. In response to various insults, microglia can develop innate immune memory (IIM), which can either enhance (priming or training) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigate whether radiation affects the IIM of microglia by irradiating the brains of rats and later exposing them to a secondary inflammatory stimulus. Comparative transcriptomic profiling and protein validation of microglia isolated from irradiated rats show a stronger immune response to a secondary inflammatory insult, demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of postmortem normal-appearing non-tumor brain tissue of patients with glioblastoma indicates that radiation-induced microglial priming is likely conserved in humans. Targeting microglial priming or avoiding further inflammatory insults could decrease radiotherapy-induced neurotoxicity.
Insights
Radiotherapy for brain tumors can cause cognitive decline by altering brain microglia. Radiation primes microglia, making them over-respond to inflammation, a finding likely relevant to human glioblastoma patients.
Area of Science:
- Neuroscience
- Immunology
- Oncology
Background:
- Radiotherapy for brain tumors frequently leads to cognitive impairment.
- Microglia, the brain's immune cells, are implicated in this neurotoxicity.
- Microglia possess innate immune memory (IIM), influencing their response to stimuli.
Purpose of the Study:
- To determine if radiotherapy alters the innate immune memory of microglia.
- To investigate the molecular mechanisms underlying radiation-induced microglial changes.
Main Methods:
- Rat brains were irradiated, followed by exposure to a secondary inflammatory stimulus.
- Comparative transcriptomic profiling and protein validation were performed on isolated microglia.
- Transcriptomic analysis of human glioblastoma patient brain tissue was conducted.
Main Results:
- Irradiated rat microglia exhibited a heightened immune response to secondary inflammatory stimuli.
- Radiation induced long-lasting molecular reprogramming in microglia.
- Evidence suggests radiation-induced microglial priming is conserved in human glioblastoma patients.
Conclusions:
- Radiotherapy can induce a persistent state of microglial priming, contributing to cognitive decline.
- Targeting microglial priming or mitigating secondary inflammation may reduce radiotherapy-induced neurotoxicity.
