Brain and Spinal Injury Center, Department of Neurological Surgery, University of California , San Francisco, CA.
Int J Radiat Biol. 2014 Mar;90(3):214-23. doi: 10.3109/09553002.2014.859761. Epub 2014 Feb 6.
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.
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.
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.
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.
放射性恐怖主义、工业事故或军事情况导致的不受控制的辐射暴露,一直是平民面临的威胁。年龄在辐射易感性方面起着重要作用;与成年人相比,年幼的儿童在发展认知能力下降方面的风险更高。我们的目的是确定辐射暴露是否会影响幼年海马体对随后发生的中度创伤性损伤的脆弱性。
3 周龄(幼年)和 8 周龄的年轻成年 C57BL/J6 雄性小鼠接受全身铯-137((137)Cs)照射,剂量为 4 格雷(Gy)。一个月后,使用皮质撞击控制系统诱导单侧创伤性脑损伤。辐射后两个月,动物在 Morris 水迷宫中进行海马依赖性认知性能测试。认知测试后,动物被安乐死,其大脑被冷冻,用于海马齿状回中激活的小胶质细胞和神经发生的免疫组织化学评估。
所有动物都能够学习水迷宫任务;但是,当评估空间记忆保留时,会出现治疗效果。作为幼鼠接受辐射,然后在一个月后接受中度创伤性脑损伤的动物没有表现出空间记忆保留,即认知受损。相比之下,所有作为成年动物治疗的组都在探测试验中表现出空间记忆保留。
尽管涉及的机制尚不清楚,但我们的结果表明,辐射增强了年轻动物在随后发生创伤性损伤后发展认知损伤的易感性。