Klin Padiatr 2013; 225 - A11
DOI: 10.1055/s-0033-1353462

Effect of ionizing irradiation on hippocampal cytokine release and neurogenesis in a murine (transgenic) tissue slice model

A Glasow 1, P Kaatzsch 1, K Eisenbruch 1, I Patties 1, F Merz 2, RD Kortmann 1, K Müller 1
  • 1Department of Radiation Therapy, University of Leipzig, Stephanstraße 9a, 04103 Leipzig, Germany
  • 2Institute of Anatomy, Liebigstraße 13, University of Leipzig, 04103 Leipzig, Germany

Radiation-induced impairment of hippocampal neurogenesis seems to play a central role in the pathogenesis of neurocognitive deficits after whole brain radiotherapy. Moreover, proinflammatory cytokines like IL-6 have been demonstrated to inhibit hippocampal neurogenesis. Here, we investigate at what radiation dose the hippocampal cytokine release and neurogenesis is affected, using a (transgenic) murine tissue slice model.

The entorhino-hippocampal formation from C57BL/J6 mice (P6) was dissected and sections transferred onto membrane inserts in six-well plates (day 1). After irradiation (0 to 4 Gy) at day 7, a potential radiogenic inflammation was determined by measuring the concentration of the cytokines IL-6, IL10, TNF, KC, MCP-1, IL12p70 and INFγ in the tissue culture supernatant 24h, 7 and 14 d after irradiation. Last, we visualized the influence of radiation exposure on hippocampal neurogenesis using transgenic Nestin-CFPnuc mice and live-imaging microscopy.

Only three (IL-6, KC and MCP-1) of the seven tested cytokines were detectable. A dose-dependent increase in cytokine release following irradiation was most pronounced at a single dose of 1.3 Gy, whereas cytokine concentration decreased again after irradiation with higher doses. The cytokine concentration in the non-irradiated cultures showed a maximum at day 1. Upon completion of wound healing (7 d after culture initiation), the cytokine concentration decreased and remained stable at a low level for at least 7 days. After irradiation with 4 Gy, we observed a reduction of nestin-positive progenitor cells in the irradiated versus non-irradiated hippocampal slice cultures of Nestin-CFPnuc mice.

Exposure to comparatively low doses increased the release of proinflammatory cytokines in hippocampal tissue cultures. The decrease of this effect at higher doses could be due to radiation-induced functional impairment or even lethal cell damage. Further studies will show whether the inflammatory changes cause or accompany radiation-induced damage to neurogenesis.