Details

Autor(en) / Beteiligte

• Prager, Isabell
• Patties, Ina
• Himmelbach, Katrin
• Kendzia, Eva
• Merz, Felicitas
• Müller, Klaus
• Kortmann, Rolf‐Dieter
• Glasow, Annegret

Titel

Dose‐dependent short‐ and long‐term effects of ionizing irradiation on neural stem cells in murine hippocampal tissue cultures: neuroprotective potential of resveratrol

Ist Teil von

• Brain and behavior, 2016-10, Vol.6 (10), p.e00548-n/a

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Introduction Radiation therapy plays an essential role in the treatment of brain tumors, but neurocognitive deficits remain a significant risk, especially in pediatric patients. In recent trials, hippocampal sparing techniques are applied to reduce these adverse effects. Here, we investigate dose‐dependent effects of ionizing radiation (IR) on juvenile hippocampal neurogenesis. Additionally, we evaluate the radioprotective potential of resveratrol, a plant polyphenol recognized for its bifunctional tumor‐preventive and anticancer effects. Methods Organotypic entorhinal–hippocampal slice cultures from transgenic nestin‐CFPnuc C57BL/J6 mice, postnatal days 3–6, were irradiated on a X‐ray machine (4.5, 8, 12, and 16 Gy, single doses) after about 2 weeks. Nestin‐positive neural stem cells were counted at a confocal live imaging microscope 0, 2, 4, 14, 25, and 42 days after IR. Resveratrol (15 μmol/L) was added 2 hr before and 24 hr after IR. Proliferation and cell death were assessed by BrdU pulse label, 48 hr after and by propidium iodide staining 96 hr after IR. GFAP‐ and NeuN‐positive cells were counted 42 days after IR in cryosectioned immunofluorescence‐stained slices. Results The observed age‐related changes of nestin‐positive stem cells in the organotypic slice culture model resembled the reduction of neural stem cells in vivo. IR (4.5–16 Gy) led to a dose‐dependent damage of the neural stem cell pool in the dentate gyrus. No recovery was seen within 42 days after doses from 4.5 Gy onward. The decline of nestin‐positive cells was paralleled by increased cell death and decreased proliferation. The number of GFAP‐positive cells was significantly enhanced. No significant change was detected in the overall NeuN‐positive cell population, whereas the number of newborn, NeuN/BrdU double‐positive neurons was reduced. Resveratrol treatment reversed the irradiation‐induced decline of neural stem cells. Conclusion The neuroprotective action of resveratrol on irradiated hippocampal tissue warrants further investigation as a possible supplement to hippocampal sparing procedures. Radiation therapy in the treatment of brain tumors often leads to neurocognitive deficits especially in pediatric patients. In organotypic entorhinal–hippocampal slice cultures, we could show that irradiation doses from 4.5 to 16 Gy, single dose, reduced the nestin‐positive neural progenitor pool irreversibly, possibly by a combinatorial effect of proliferation inhibition, cell death induction, and aberrant differentiation. Resveratrol was able to partially reverse the irradiation‐induced decline of progenitor cells, indicating some neuroprotective potential.