Brain and Spinal Injury Center, University of California, San Francisco, California 94110, USA.
Hippocampus. 2012 Mar;22(3):544-54. doi: 10.1002/hipo.20920. Epub 2010 Dec 29.
Exposure to ionizing irradiation may affect brain functions directly, but may also change tissue sensitivity to a secondary insult such as trauma, stroke, or degenerative disease. To determine if a low dose of particulate irradiation sensitizes the brain to a subsequent injury, C56BL6 mice were exposed to brain only irradiation with 0.5 Gy of (56) Fe ions. Two months later, unilateral traumatic brain injury was induced using a controlled cortical impact system. Three weeks after trauma, animals received multiple BrdU injections and 30 days later were tested for cognitive performance in the Morris water maze. All animals were able to locate the visible and hidden platform during training; however, treatment effects were seen when spatial memory retention was assessed in the probe trial (no platform). Although sham and irradiated animals showed spatial memory retention, mice that received trauma alone did not. When trauma was preceded by irradiation, performance in the water maze was not different from sham-treated animals, suggesting that low-dose irradiation had a protective effect in the context of a subsequent traumatic injury. Measures of hippocampal neurogenesis showed that combined injury did not induce any changes greater that those seen after trauma or radiation alone. After trauma, there was a significant decrease in the percentage of neurons expressing the behaviorally induced immediate early gene Arc in both hemispheres, without associated neuronal loss. After combined injury there were no differences relative to sham-treated mice. Our results suggest that combined injury resulted in decreased alterations of our endpoints compared to trauma alone. Although the underlying mechanisms are not yet known, these results resemble a preconditioning, adaptive, or inducible-like protective response, where a sublethal or potentially injurious stimulus (i.e., irradiation) induces tolerance to a subsequent and potentially more damaging insult (trauma).
电离辐射暴露可能直接影响大脑功能，但也可能改变组织对二次损伤（如创伤、中风或退行性疾病）的敏感性。为了确定低剂量颗粒辐射是否会使大脑对随后的损伤敏感，C56BL6 小鼠接受了 0.5 Gy 的（56）Fe 离子脑照射。两个月后，使用皮质撞击控制系统诱导单侧创伤性脑损伤。创伤后 3 周，动物接受多次 BrdU 注射，30 天后在 Morris 水迷宫中进行认知性能测试。所有动物都能够在训练过程中找到可见和隐藏的平台；然而，在探针试验（无平台）中评估空间记忆保留时，观察到治疗效果。虽然假手术和照射组动物表现出空间记忆保留，但单独接受创伤的动物没有。当创伤前先进行照射时，水迷宫中的表现与假手术处理的动物没有区别，这表明低剂量照射在随后的创伤性损伤中有保护作用。海马神经发生的测量表明，联合损伤不会引起比单独创伤或照射更大的变化。创伤后，两侧半球表达行为诱导的早期基因 Arc 的神经元比例显著下降，而没有伴随神经元丢失。联合损伤后，与假手术处理的小鼠相比没有差异。我们的结果表明，与单独创伤相比，联合损伤导致我们的终点变化减少。虽然潜在的机制尚不清楚，但这些结果类似于预处理、适应性或诱导性保护反应，其中亚致死或潜在的损伤性刺激（即照射）诱导对随后潜在更具破坏性的损伤（创伤）的耐受。
