Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, Sweden.
Dev Neurosci. 2013;35(5):406-15. doi: 10.1159/000353820. Epub 2013 Aug 20.
Radiotherapy is an effective treatment strategy in the treatment of brain tumors, but it is also a major cause of long-term complications, especially in survivors of pediatric brain tumors. Cognitive decline caused by cranial radiotherapy is thought, at least partly, to depend on injury to stem and progenitor cells in the dentate gyrus of the hippocampus. This study investigated the effects of lipopolysaccharide (LPS)-induced inflammation at the time of irradiation (IR) in the growing mouse brain. A single injection of LPS (0.3 mg/kg) was administered 24 h prior to cranial IR of 14-day-old male mice. LPS pretreatment increased the levels of the chemokine CCL2 and the cytokine IL-1β in the brain by 440 and 560%, respectively, compared to IR alone. IR disrupted hippocampal neurogenesis and the growth of the dentate gyrus, and the mice pretreated with LPS displayed an even more pronounced lack of growth than the vehicle-treated group 2 months after IR. The density of microglia was not affected, but LPS-pretreated mice displayed 48% fewer bromodeoxyuridine-positive cells and 43% fewer doublecortin-positive cells in the granule cell layer 2 months after IR compared with the vehicle-treated group. In conclusion, an ongoing inflammation in the brain at the time of IR further enhanced the IR-induced loss of neurogenesis, and may aggravate future cognitive deficits in patients treated with cranial radiotherapy.
放射治疗是治疗脑肿瘤的有效治疗策略，但也是长期并发症的主要原因，尤其是在儿童脑肿瘤幸存者中。颅放射治疗引起的认知能力下降被认为至少部分取决于海马齿状回中的干细胞和祖细胞损伤。本研究调查了照射时脂多糖 (LPS) 诱导的炎症对生长中的小鼠大脑的影响。在 14 天大的雄性小鼠颅放射治疗前 24 小时，单次注射 LPS（0.3 mg/kg）。与单独照射相比，LPS 预处理使趋化因子 CCL2 和细胞因子 IL-1β 的水平分别增加了 440%和 560%。IR 破坏了海马神经发生和齿状回的生长，用 LPS 预处理的小鼠在 IR 后 2 个月显示出比载体处理组更明显的生长缺乏。小胶质细胞密度没有受到影响，但与载体处理组相比，LPS 预处理组的 BrdU 阳性细胞和双皮质素阳性细胞在颗粒细胞层中分别减少了 48%和 43%。总之，IR 时大脑中的持续炎症进一步增强了 IR 诱导的神经发生丧失，并可能加重接受颅放射治疗的患者未来的认知缺陷。
