Early effects on the cognitive function and microvessel density after local brain irradiation with carbon ions

脑功能障碍是与脑肿瘤和急性淋巴细胞白血病的放射治疗相关的主要问题之一。据报道，在癌症治疗期间暴露于辐射后，中枢神经系统（CNS）组织会出现学习障碍和认知功能障碍等副作用。本研究探讨了碳离子局部脑照射对小鼠认知功能和微血管密度（MVD）的早期影响。用日本千叶重离子医用加速器产生的290 MeV/u 5 mm SOBP碳束进行辐照。除眼和脑干外，全脑照射。10-30戈伊单次照射组小鼠在照射后36 h出现短时记忆功能障碍，而碳源照射组小鼠在长时记忆功能无障碍，照射后1周组织学检查未见异常。尽管在照射后16周，照射小鼠在海马CA 1至CA 3层内显示出明显的神经元变性。照射组海马CA 1 -3区神经细胞减少30- 49%。照射后1周，海马和大脑皮质的MVD迅速下降。脑微血管密度在1 ~ 12周也呈下降趋势，放射性血管病变一般呈剂量和时间依赖性。放射性神经元的变性可能与血管损伤后的缺血机制相同。

Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors and acute lymphoblastic leukemia. Side effects such as learning impairment and cognitive dysfunction are reported on the central nervous system (CNS) tissue after exposure to radiation during cancer therapy. This study investigated early effects on the cognitive function and microvessel density (MVD) after local brain irradiation with carbon ions using mice. Irradiation was carried out a 290 MeV/u 5 mm-SOBP carbon beam produced by the Heavy Ions Medical Accelerator in Chiba, Japan. The whole of brain was irradiated, excluding eyes and brain stem. The mice irradiated with single dose of 10-30 Gy showed deficit in short-term working memory assessed at 36 hr after irradiation, whereas mice receiving carbon irradiation showed no deficit in long-term memory.Histopathological observation revealed no abnormal finding in the irradiated brain at 1 week after irradiation, although irradiated mice showed marked neuronal degeneration at the hippocampus within CA1 to CA3 layers at 16 weeks after irradiation. In the irradiated group, neuronal cells in the hippocampal CA1-3 areas were reduced by 30-49%. However, MVD of the hippocampus and cerebral cortex decreased rapidly from 1 week after irradiation. The cerebral MVD also declined from 1 to 12 weeks and radiation vasculopathy generally was dose and time dependent. It is possibility that radiation-induced degeneration of neuronal cells caused by same mechanism as the ischemia follow vasculature breakdown.