Whole-brain irradiation increases NREM sleep and hypothalamic expression of IL-1β in rats

Abstract

Purpose: Although it has mainly been described qualitatively, whole brain irradiation induces somnolence in patients with malignant diseases. Therefore, we used a rat model to quantify the effects of irradiation of healthy brain tissue on both sleep-wake patterns and the expression of the pro-inflammatory cytokine interleukin-1β (IL-1β), which is known to induce sleep.

Materials and methods: Different groups were examined at three time points after irradiation (1 day, 30 days and 60 days). Polysomnographic recordings were performed on each rat before and after total cranial irradiation (12 Gy). IL-1β protein levels in several brain regions were assessed by enzyme-linked immunosorbent assays, and site-specific immunoreactivity was observed by immunofluorescence.

Results: We found that both non-rapid eye movement sleep and IL-1β protein expression in the hypothalamus increased 30 days after irradiation.

Conclusions: Whole brain irradiation increases sleep in our rat model, and this finding is similar to qualitative reports from patients. Because IL-1β has been proposed as a sleep-promoting molecule, we propose that the polysomnographic results may be attributable, at least in part, to the delayed overexpression of IL-1β in the hypothalamus.

Keywords::

• Whole brain irradiation
• sleep
• neuro-inflammation
• IL-1β
• hypothalamus
• median preoptic area

Acknowledgements

This paper constitutes a partial fulfillment of the Graduate Program in Biomedical Sciences of the National Autonomous University of Mexico (UNAM). We would like to thank S. Moreno Jiménez and J. M. Lárraga Gutiérrez for their support and facilitation of the Radiosurgery Unit resources. We also would like to thank J. Guevara Fonseca for the use of the microscope and J. Hernández Falcón for his valuable comments on this work.

Declaration of interest

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