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@ARTICLE{Hegering:303086,
      author       = {R. Hegering and S. Nexhipi$^*$ and T. Suckert$^*$ and J.
                      Soltwedel and E. Beyreuther and M. Krause$^*$ and A.
                      Dietrich$^*$ and A. Lühr},
      title        = {{R}adiation-induced changes of reactive astrocyte
                      distribution in mice as a late response to partial-brain
                      proton irradiation.},
      journal      = {Acta oncologica},
      volume       = {64},
      issn         = {0284-186X},
      address      = {Abingdon},
      publisher    = {Taylor $\&$ Francis Group},
      reportid     = {DKFZ-2025-01511},
      pages        = {902 - 908},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Animals / Astrocytes: radiation effects / Astrocytes:
                      pathology / Astrocytes: metabolism / Mice / Proton Therapy:
                      adverse effects / Proton Therapy: methods / Mice, Inbred
                      C57BL / Glial Fibrillary Acidic Protein: metabolism / Brain
                      Neoplasms: radiotherapy / Brain Neoplasms: pathology /
                      Blood-Brain Barrier: radiation effects / Brain: radiation
                      effects / Brain: pathology / Cranial Irradiation: adverse
                      effects / Hippocampus: radiation effects / Hippocampus:
                      pathology / Male / Dose-Response Relationship, Radiation /
                      Radiotherapy Dosage / Cone-Beam Computed Tomography / Glial
                      Fibrillary Acidic Protein (NLM Chemicals) / glial fibrillary
                      astrocytic protein, mouse (NLM Chemicals)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40697178},
      doi          = {10.2340/1651-226X.2025.44056},
      url          = {https://inrepo02.dkfz.de/record/303086},
}