Hypothermia after cranial irradiation protects neural progenitor cells in the subventricular zone but not in the hippocampus

Abstract

Purpose: To explore if hypothermia can reduce the harmful effects of ionizing radiation on the neurogenic regions of the brain in young rats.

Materials and methods: Postnatal day 9 rats were randomized into two treatment groups, hypo- and normothermia, or a control group. Treatment groups were placed in chambers submerged in temperature-controlled water baths (30 °C and 36 °C) for 8 h, after receiving a single fraction of 8 Gy to the left hemisphere. Seven days’ post-irradiation, we measured the sizes of the subventricular zone (SVZ) and the granule cell layer (GCL) of the hippocampus, and counted the number of proliferating (phospho-histone H3+) cells and microglia (Iba1 + cells).

Results: Irradiation caused a 53% reduction in SVZ size in the normothermia group compared to controls, as well as a reduction of proliferating cell numbers by >50%. These effects were abrogated in the hypothermia group. Irradiation reduced the number of microglia in both treatment groups, but resulted in a lower cell density of Iba1 + cells in the SVZs of the hypothermia group. In the GCL, irradiation decreased both GCL size and the proliferating cell numbers, but with no difference between the treatment groups. The number of microglia in the GCL did not change.

Conclusions: Hypothermia immediately after irradiation protects the SVZ and its proliferative cell population but the GCL is not protected, one week post-irradiation.

Keywords:

• Radiotherapy
• neurogenesis
• granule cell layer
• Iba1
• phospho-histone H3
• brain

Acknowledgements

We are grateful for the skillful technical assistance of Rita Grandér.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Notes on contributors

Magnus Sabel is a consultant pediatric oncologist at the Childhood Cancer Center at Queen Silvia Children’s Hospital in Gothenburg and a researcher at the University of Gothenburg.

Marie Kalm is an assistant professor at the department of pharmacology, University of Gothenburg. Her research is focused on foreseeing and preventing the chronic neurodegenerative state following cranial radiotherapy.

Birgitta Lannering is professor of pediatric oncology at the University of Gothenburg and senior consultant at the Queen Silvia Children?s Hospital in Gothenburg. Her research concerns children with brain tumors.

Thomas Björk-Eriksson is academic senior consultant as well as associate professor at the Sahlgrenska Academy in Gothenburg, Sweden. Presently he is head of Regional Cancer Center in the Western Region, Sweden. His main focus is radiation therapy including radiation biology, technique improvements and understanding and preventing long time side effects.

Klas Blomgren is professor of pediatrics at the Karolinska Institute, and pediatric oncologist at the Karolinska University Hospital. His research is focused on ameliorating the negative effects of radiotherapy on the juvenile brain.

Additional information

Funding

This work was supported by the Swedish Research Council under Grant (no. 2003-4723 to KB), the Swedish Childhood Cancer Foundation under Grant (no. PROJ05-076 to KB), Governmental grants to scientists working in health care (ALF) in Gothenburg, the Frimurare Barnhusfonden, and the Swedish Cancer Foundation.