TY  - JOUR
AU  - Hegering, Robin
AU  - Nexhipi, Sindi
AU  - Suckert, Theresa
AU  - Soltwedel, Johannes
AU  - Beyreuther, Elke
AU  - Krause, Mechthild
AU  - Dietrich, Antje
AU  - Lühr, Armin
TI  - Radiation-induced changes of reactive astrocyte distribution in mice as a late response to partial-brain proton irradiation.
JO  - Acta oncologica
VL  - 64
SN  - 0284-186X
CY  - Abingdon
PB  - Taylor & Francis Group
M1  - DKFZ-2025-01511
SP  - 902 - 908
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Astrocytes: radiation effects
KW  - Astrocytes: pathology
KW  - Astrocytes: metabolism
KW  - Mice
KW  - Proton Therapy: adverse effects
KW  - Proton Therapy: methods
KW  - Mice, Inbred C57BL
KW  - Glial Fibrillary Acidic Protein: metabolism
KW  - Brain Neoplasms: radiotherapy
KW  - Brain Neoplasms: pathology
KW  - Blood-Brain Barrier: radiation effects
KW  - Brain: radiation effects
KW  - Brain: pathology
KW  - Cranial Irradiation: adverse effects
KW  - Hippocampus: radiation effects
KW  - Hippocampus: pathology
KW  - Male
KW  - Dose-Response Relationship, Radiation
KW  - Radiotherapy Dosage
KW  - Cone-Beam Computed Tomography
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - glial fibrillary astrocytic protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40697178
DO  - DOI:10.2340/1651-226X.2025.44056
UR  - https://inrepo02.dkfz.de/record/303086
ER  -