Time-course of hypothalamic-pituitary-adrenal axis activity and inflammation in juvenile rat brain after cranial irradiation

Recent studies reported that exposure of juvenile rats to cranial irradiation affects hypothalamic-pituitary- adrenal (HPA) axis stability, leading to its activation along with radiation-induced inflammation. In the present study, we hypothesized whether inflammatory reaction in the CNS could be a mediator of HPA axis response to cranial irradiation (CI). Therefore, we analyzed time- course changes of serum corticosterone level, as well IL-1b and TNF-a level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NFjB) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NFjB mRNA and protein in the hippocampus at 1 h. The increment in NFjB protein persisted for 2 h, therefore NFjB/GR protein ratio was turned in favor of NFjB. Central inflammation was characterized by increased IL-1b in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1b and TNF-a were undetectable in the serum. Enhanced hypothalamic IL-1b probably induced the relocation of hippocampal NFjB to the nucleus and decreased NFjB mRNA at 6 h, indicating promotion of inflammation in the key tissue for HPA axis regulation. Concomitant increase of corticosterone level and enhanced GR nuclear translocation in the hippocampus at 6 h might represent a compensatory mechanism for observed inflammation. Our results indicate that acute radiation response is characterized by increased central inflammation and concomitant HPA axis activation, most likely having a role in protection of the organism from overwhelming inflammatory reaction.