title: Delayed effects of brain irradiation--part 1: adrenocortical axis dysfunction and hippocampal damage in an adult rat model.
abstract: BACKGROUND
  Brain irradiation (BI) in humans may cause behavioral changes, cognitive impairment and neuroendocrine dysfunction. The effect of BI on the hypothalamic-pituitary-adrenal (HPA) axis is not fully understood.
  
  
  OBJECTIVE
  To evaluate the effect of BI on HPA axis responses under basal and stressful conditions as well as following pretreatment with dexamethasone (Dex).
  
  
  METHODS
  Adult male rats were exposed to whole BI. HPA axis responses were examined at 2, 4, 9 and 20 weeks after BI. Histological evaluations of the irradiated rats and matched controls were conducted at 4 and 20 weeks after BI.
  
  
  RESULTS
  In contrast to the control group, the basal and stress-induced corticosterone levels were enhanced at 9 and 20 weeks after BI and the inhibitory effect of Dex was reduced. BI also caused hyposuppression of the adrenocortical response to stress. Histological assessment of the irradiated brains revealed hippocampal atrophy at 20 weeks after BI. The neuronal counts were lower only in the CA1 region of the irradiated brains. BI caused a decrease in the binding capacity of Dex to the hippocampal cytosolic fraction.
  
  
  CONCLUSIONS
  Enhanced stress-induced HPA axis responses and the reduced effect of Dex suggest that BI has delayed effects on HPA axis responses as manifested by impairment of the negative feedback exerted by glucocorticoids (GCs). The mechanisms underlying these effects of BI are unknown. It is possible that the marked BI-induced damage in the hippocampus, which plays an important role in the regulation of the feedback effect of GCs, may cause abnormal HPA axis responses following BI.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Joseph
authors.initials: J
authors.lastname: Weidenfeld
authors.forename: Tali
authors.initials: T
authors.lastname: Siegal
authors.forename: Haim
authors.initials: H
authors.lastname: Ovadia
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D016371:Cranial Irradiation / Q000009:adverse effects*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000503:physiopathology / Q000528:radiation effects*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D007150:Immunohistochemistry; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology / Q000528:radiation effects*; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological / Q000502:physiology; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone