%0 Journal Article
%A Hegering, Robin
%A Nexhipi, Sindi
%A Suckert, Theresa
%A Soltwedel, Johannes
%A Beyreuther, Elke
%A Krause, Mechthild
%A Dietrich, Antje
%A Lühr, Armin
%T Radiation-induced changes of reactive astrocyte distribution in mice as a late response to partial-brain proton irradiation.
%J Acta oncologica
%V 64
%@ 0284-186X
%C Abingdon
%I Taylor & Francis Group
%M DKFZ-2025-01511
%P 902 - 908
%D 2025
%X After 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.Previously, 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.For 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.GFAP upregulation correlated with dose level and distribution. In combination with other markers and timepoints, these findings contribute to a comprehensive understanding of cellular response.
%K Animals
%K Astrocytes: radiation effects
%K Astrocytes: pathology
%K Astrocytes: metabolism
%K Mice
%K Proton Therapy: adverse effects
%K Proton Therapy: methods
%K Mice, Inbred C57BL
%K Glial Fibrillary Acidic Protein: metabolism
%K Brain Neoplasms: radiotherapy
%K Brain Neoplasms: pathology
%K Blood-Brain Barrier: radiation effects
%K Brain: radiation effects
%K Brain: pathology
%K Cranial Irradiation: adverse effects
%K Hippocampus: radiation effects
%K Hippocampus: pathology
%K Male
%K Dose-Response Relationship, Radiation
%K Radiotherapy Dosage
%K Cone-Beam Computed Tomography
%K Glial Fibrillary Acidic Protein (NLM Chemicals)
%K glial fibrillary astrocytic protein, mouse (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40697178
%R 10.2340/1651-226X.2025.44056
%U https://inrepo02.dkfz.de/record/303086