title: Radiation exposure prior to traumatic brain injury induces responses that differ as a function of animal age.
abstract: OBJECTIVE
  Uncontrolled radiation exposure due to radiological terrorism, industrial accidents or military circumstances is a continuing threat for the civilian population. Age plays a major role in the susceptibility to radiation; younger children are at higher risk of developing cognitive deterioration when compared to adults. Our objective was to determine if an exposure to radiation affected the vulnerability of the juvenile hippocampus to a subsequent moderate traumatic injury.
  
  
  METHODS
  Three-week-old (juvenile) and eight-week-old young adult C57BL/J6 male mice received whole body cesium-137 ((137)Cs) irradiation with 4 gray (Gy). One month later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Two months post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water-maze. After cognitive testing, animals were euthanized and their brains frozen for immunohistochemical assessment of activated microglia and neurogenesis in the hippocampal dentate gyrus.
  
  
  RESULTS
  All animals were able to learn the water maze task; however, treatment effects were seen when spatial memory retention was assessed. Animals that received irradiation as juveniles followed by a moderate traumatic brain injury one month later did not show spatial memory retention, i.e., were cognitively impaired. In contrast, all groups of animals that were treated as adults showed spatial memory retention in the probe trials.
  
  
  CONCLUSIONS
  Although the mechanisms involved are not clear, our results suggest that irradiation enhanced a young animal's vulnerability to develop cognitive injury following a subsequent traumatic injury.
authors.affiliation: Brain and Spinal Injury Center, Department of Neurological Surgery, University of California , San Francisco, CA.
authors.forename: Antiño R
authors.initials: AR
authors.lastname: Allen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Eilertson
authors.forename: Ayanabha
authors.initials: A
authors.lastname: Chakraborti
authors.forename: Sourabh
authors.initials: S
authors.lastname: Sharma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baure
authors.forename: Julian
authors.initials: J
authors.lastname: Habdank-Kolaczkowski
authors.forename: Barrett
authors.initials: B
authors.lastname: Allen
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: John R
authors.initials: JR
authors.lastname: Fike
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000528:radiation effects; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology*; D003071:Cognition / Q000528:radiation effects; D018891:Dentate Gyrus / Q000473:pathology; D006624:Hippocampus / Q000528:radiation effects; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D018782:Maze Learning / Q000528:radiation effects; D008568:Memory / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D011832:Radiation Injuries / Q000150:complications*