Bálentová Soňa, Hnilicová Petra, Kalenská Dagmar, Murín Peter, Hajtmanová Eva, Lehotský Ján, Adamkov Marian
Institute of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4, 036 01 Martin, Slovak Republic.
Division of Neurosciences, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4D, 036 01 Martin, Slovak Republic.
Neurotoxicology. 2017 May;60:70-81. doi: 10.1016/j.neuro.2017.03.005. Epub 2017 Mar 19.
Effect of ionizing radiation on the brain affects neuronal, glial, and endothelial cell population and lead to significant morphological, metabolic, and functional deficits. In the present study we investigated a dose- and time-dependent correlation between radiation-induced metabolic and histopathological changes. Adult male Wistar rats received a total dose of 35Gy delivered in 7 fractions (dose 5Gy per fraction) once per week in the same weekday during 7 consecutive weeks. Proton magnetic resonance spectroscopy (H MRS), histochemistry, immunohistochemistry and confocal microscopy were used to determine whether radiation-induced alteration of the brain metabolites correlates with appropriate histopathological changes of neurogenesis and glial cell response in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone-olfactory bulb axis (SVZ-OB axis). Evaluation of the brain metabolites 18-19 weeks after irradiation performed by H MRS revealed a significant decrease in the total N-acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum and OB. A significant decline of gamma-aminobutyric acid to tCr (GABA/tCr) ratio was seen in the OB and hippocampus. MR revealed absence of gross inflammatory or necrotic lesions in these regions. Image analysis of the brain sections 18-21 weeks after the exposure showed a radiation-induced increase of neurodegeneration, inhibition of neurogenesis and strong resemblance to the reactive astrogliosis. Results showed that fractionated whole-brain irradiation led to the changes in neurotransmission and to the loss of neuronal viability in vivo. Metabolic changes were closely associated with histopathological findings, i.e. initiation of neuronal cell death, inhibition of neurogenesis and strong response of astrocytes indicated development of late radiation-induced changes.
电离辐射对大脑的影响涉及神经元、神经胶质细胞和内皮细胞群体，并导致显著的形态、代谢和功能缺陷。在本研究中，我们调查了辐射诱导的代谢变化与组织病理学变化之间的剂量和时间依赖性相关性。成年雄性Wistar大鼠在连续7周的同一工作日每周接受一次总剂量为35Gy的分次照射（每次剂量为5Gy，共7次）。采用质子磁共振波谱（H MRS）、组织化学、免疫组织化学和共聚焦显微镜来确定辐射诱导的脑代谢物改变是否与两个神经发生区域（海马齿状回（DG）和脑室下区-嗅球轴（SVZ-OB轴））神经发生和神经胶质细胞反应的相应组织病理学变化相关。照射后18-19周通过H MRS对脑代谢物进行评估，结果显示纹状体和嗅球中总N-乙酰天门冬氨酸与总肌酸（tNAA/tCr）比值显著降低。在嗅球和海马中观察到γ-氨基丁酸与tCr（GABA/tCr）比值显著下降。磁共振成像显示这些区域不存在明显的炎症或坏死性病变。照射后18-21周对脑切片进行图像分析，结果显示辐射诱导神经退行性变增加、神经发生受到抑制，且与反应性星形胶质细胞增生极为相似。结果表明，分次全脑照射导致体内神经传递发生变化以及神经元活力丧失。代谢变化与组织病理学结果密切相关，即神经元细胞死亡的起始、神经发生的抑制以及星形胶质细胞的强烈反应表明发生了晚期辐射诱导变化。
