ArticleActa oncologica (Stockholm, Sweden)2025
Radiation-induced changes of reactive astrocyte distribution in mice as a late response to partial-brain proton irradiation.
Article in Acta oncologica (Stockholm, Sweden), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Six-month evaluation of normal mouse brain side effects: Comparing FLASH and conventional proton partial brain irradiation.Clinical and translational radiation oncology · 2026Article
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
background and purposeAfter proton therapy of brain tumors, several studies have reported late image changes in follow-up magnetic resonance imaging, which result from blood-brain barrier (BBB) disruption. Astrocytes play a central role in the formation and maintenance of the BBB. To study the late response to partial-brain proton irradiation, preclinical mouse data were utilized to investigate the spatial distribution and dose dependence of reactive astrocytes. MATERIAL AND
methodsPreviously, C57BL/6JRj mice were irradiated with protons targeting the right hippocampal region with single prescription doses of 45-85 Gy. After six months, mice were sacrificed and the excised brains axially cut into 3 µm thick slices and stained for glial fibrillary acidic protein (GFAP) to target astrocytes. Here, a workflow to segment the GFAP-positive area on slice images was established. The fraction of GFAP-positive area (GFAP+ fraction) was evaluated in the high-dose region in the right hemisphere and in the mirrored region in the left hemisphere. Dose distributions were simulated on pre-irradiation cone-beam computed tomography and co-registered to the histological slices.
resultsFor all irradiated mice, the GFAP+ fraction in the right hemisphere was significantly increased compared to the left hemisphere and to a sham-irradiated mouse with a highly symmetric GFAP distribution. The GFAP+ fraction in the right hemisphere increased approximately linearly with prescription dose. For comparable doses, the cerebral cortex showed lower GFAP+ fractions than the midbrain.
interpretationGFAP upregulation correlated with dose level and distribution. In combination with other markers and timepoints, these findings contribute to a comprehensive understanding of cellular response.
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