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Titel: Region-Specific Effects of Fractionated Low-Dose Versus Single-Dose Radiation on Hippocampal Neurogenesis and Neuroinflammation
VerfasserIn: Schmal, Zoé
Rübe, Claudia E.
Sprache: Englisch
Titel: Cancers
Bandnummer: 14
Heft: 22
Verlag/Plattform: MDPI
Erscheinungsjahr: 2022
Freie Schlagwörter: radiotherapy
radiosensitivity
hippocampus
neurogenesis
neuroinflammation
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Background: Despite technical advances in hippocampus-sparing radiotherapy, radiationinduced injury to neural stem cell compartments may affect neurocognitive functions. In pre-clinical mouse models with fractionated low-dose radiation (FLDR) and single-dose radiation (SDR), the accurate response to radiation-induced injury was analyzed in different hippocampal subregions. Methods: Adult and juvenile C57BL/6NCrl mice were exposed to FLDR (20 × 0.1 Gy, daily exposure from Monday to Friday for 4 weeks) or SDR (1 × 2 Gy). In addition, 72 h after the last exposure, neuroglia (astrocytes and microglia) and neuroprogenitor cells were characterized and quantified in the hippocampal cornu ammonis (CA) and dentate gyrus (DG) by immunofluorescence studies. Results: After analyzing different hippocampal subregions, it was observed that radiation responses varied between non-neurogenic CA, with no detectable inflammatory alterations, and neurogenic DG, characterized by impaired neurogenesis and subsequent neuroinflammation. Age-dependent differences in radiosensitivity appeared to depend on the varying proliferative potential of neural stem cell niches. Using the same overall dose for FLDR and SDR (2 Gy), both the cumulative dose over time and also the single dose fraction have decisive impacts on hippocampal damage. Conclusion: Region-specific effects of radiation-induced hippocampal injury relies primarily on cell deaths of proliferating neuroprogenitors. Dose per fraction defines the extent of neuronal injury, and subsequently activated microglia and reactive astrocytes modulate dynamic processes of neuroinflammation. Thus, limiting both cumulative doses and dose fractions to hippocampal DG is an important issue of clinical radiotherapy to preserve neurocognitive functions.
DOI der Erstveröffentlichung: 10.3390/cancers14225477
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-382138
hdl:20.500.11880/34499
http://dx.doi.org/10.22028/D291-38213
ISSN: 2072-6694
Datum des Eintrags: 25-Nov-2022
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Radiologie
Professur: M - Prof. Dr. Christian Rübe
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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