title: Time-course of hypothalamic-pituitary-adrenal axis activity and inflammation in juvenile rat brain after cranial irradiation.
abstract: 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-1β and TNF-α level in the serum and hypothalamus of juvenile rats after CI. Protein and gene expression of the glucocorticoid receptor (GR) and nuclear factor kappaB (NFκB) were examined in the hippocampus within 24 h postirradiation interval. Cranial irradiation led to rapid induction of both GR and NFκB mRNA and protein in the hippocampus at 1 h. The increment in NFκB protein persisted for 2 h, therefore NFκB/GR protein ratio was turned in favor of NFκB. Central inflammation was characterized by increased IL-1β in the hypothalamus, with maximum levels at 2 and 4 h after irradiation, while both IL-1β and TNF-α were undetectable in the serum. Enhanced hypothalamic IL-1β probably induced the relocation of hippocampal NFκB to the nucleus and decreased NFκB 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.
authors.affiliation: Department of Biochemistry, Institute for Biological Research Siniša Stanković, Belgrade, Serbia. nvelickovic@ibiss.bg.ac.rs
authors.forename: Nataša
authors.initials: N
authors.lastname: Veličković
authors.forename: Dunja
authors.initials: D
authors.lastname: Drakulić
authors.forename: Snježana
authors.initials: S
authors.lastname: Petrović
authors.forename: Ivana
authors.initials: I
authors.lastname: Grković
authors.forename: Maja
authors.initials: M
authors.lastname: Milošević
authors.forename: Miloš
authors.initials: M
authors.lastname: Stanojlović
authors.forename: Anica
authors.initials: A
authors.lastname: Horvat
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D016371:Cranial Irradiation / Q000009:adverse effects*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors