title: Systemic effects of fractionated, whole-brain irradiation in young adult and aging rats.
abstract: Cranial irradiation is a critical and effective treatment for primary brain tumors and metastases. Unfortunately, most patients who are treated and survive for more than a few months develop neural and cognitive problems as the result of radiation-induced normal tissue injury. The neurobiological mechanisms underlying these cognitive deficits remain largely unknown and there are no validated treatments to prevent or ameliorate them; thus, there is a significant and continuing need for preclinical studies in animal models. Investigations from several laboratories have demonstrated neurobiological changes after cranial irradiation in rodents. To date, however, experimental studies in animal models have included little assessment of the systemic effects of cranial irradiation, despite evidence from the clinic that cranial irradiation results in changes throughout the body and recognition that systemic responses may influence the development of neural and cognitive deficits. This study evaluated systemic effects of clinically relevant, fractionated whole-brain irradiation in adult rats and demonstrates effects on the growth hormone/insulin-like growth factor-I axis, which may contribute to the development of neural changes. These and other systemic responses are important to consider in ongoing efforts to understand the mechanisms of radiation-induced normal tissue injury.
authors: a Departments of Neurobiology and Anatomy and.
authors: M E
authors: ME
authors: Forbes
authors: M
authors: M
authors: Paitsel
authors: J D
authors: JD
authors: Bourland
authors: D R
authors: DR
authors: Riddle
mesh_terms: D000375:Aging; D000818:Animals; D001921:Brain / Q000473:pathology / Q000528:radiation effects*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D016371:Cranial Irradiation; D019583:Dose Fractionation, Radiation; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010902:Pituitary Gland / Q000473:pathology / Q000528:radiation effects; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
references: Int J Radiat Oncol Biol Phys. 2006 Nov 1;66(3):860-6
references: 17011458
references: Sci Rep. 2012;2:250
references: 22355762
references: Curr Treat Options Oncol. 2006 Nov;7(6):517-23
references: 17032563
references: Radiother Oncol. 2011 Apr;99(1):23-8
references: 21458091
references: Neuro Oncol. 2012 Sep;14 Suppl 4:iv37-44
references: 23095829
references: J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B54-9
references: 8548501
references: Endocrinology. 2007 Aug;148(8):3765-72
references: 17510237
references: Radiat Res. 2011 Oct;176(4):459-73
references: 21787181
references: Br J Pharmacol. 2009 Jul;157(6):881-91
references: 19438508
references: Eur J Cancer. 2001 Oct;37(15):1938-45
references: 11576851
references: Endocr Dev. 2009;15:1-24
references: 19293601
references: Neuroscientist. 2009 Apr;15(2):134-48
references: 19307421
references: Neuroscience. 2001;107(4):603-13
references: 11720784
references: J Neurosci Res. 2006 Feb 1;83(2):199-210
references: 16385581
references: Exp Brain Res. 2010 Apr;201(4):781-7
references: 19943037
references: Glia. 2009 Aug 1;57(10):1062-71
references: 19115393
references: Mech Ageing Dev. 2006 Jan;127(1):57-63
references: 16243379
references: Eur J Endocrinol. 2009 Nov;161 Suppl 1:S97-S106
references: 19684058
references: Brain Res Dev Brain Res. 2002 Mar 31;134(1-2):115-22
references: 11947942
references: Br J Radiol. 1989 Aug;62(740):679-94
references: 2670032
references: J Endocrinol. 2001 Jun;169(3):519-26
references: 11375122
references: Exp Gerontol. 2009 Jan-Feb;44(1-2):10-9
references: 18675334