show Abstracthide AbstractFractionated whole-brain irradiation for the treatment of intracranial neoplasia causes progressive neurodegeneration and neuroinflammation. The long-term consequences of high single dose brain irradiation are unknown. In order to assess the late effects of brain irradiation we have compared transcriptomic gene expression profiles from nonhuman primates (rhesus macaques, Macaca mulatta) receiving single dose total body irradiation to those given fractionated whole brain radiotherapy and control comparators. Gene expression profiles from the dorsolateral prefrontal cortex (Brodmann area 46), hippocampus, and deep white matter (centrum semiovale) were compared. The goals of this study were to identify novel potential molecular effects of radiation-induced brain injury, to evaluate regional differences in the cerebral radiation response, and to assess whether animals receiving high dose total body irradiation demonstrated similar transcriptomic patterns as those observed in animals receiving fractionated whole brain irradiation. Overall design: 3x3 design in which 3 brain regions [dorsolateral prefrontal cortex (brodmann area 46), hippocampus, and deep whiter matter (centrum semiovale)] were evaluated from three treatment groups: thorax-only irradiated control animals (10 Gy, estimated dose to the brain < 0.1 Gy), animals receiving fractionated whole brain irradiation (n=5, 40 Gy, 8x5 Gy fractions; 12 months prior to necropsy) and animals receiving high, single dose, total body irradiation (n=5, 6.75 - 8.05 Gy, 6-9 years prior to necropsy). The effects of brain region and irradiation status on differential gene expression were evaluated.