Bálentová Soňa, Hajtmanová Eva, Filová Barbora, Borbélyová Veronika, Lehotský Ján, Adamkov Marian
a Institute of Histology and Embryology, Jessenius Faculty of Medicine , Comenius University in Bratislava , Martin , Slovak Republic.
b Department of Radiotherapy and Oncology , Martin University Hospital , Martin , Slovak Republic.
Int J Radiat Biol. 2018 Mar;94(3):238-247. doi: 10.1080/09553002.2018.1425805. Epub 2018 Jan 23.
The aim of this study was investigate whether histopathological changes in the neurogenic region correlate with appropriate cognitive impairment in the experimental model of radiation-induced brain injury.
Adult male Wistar rats randomized into sham (0 Gy) and two experimental groups (survived 30 and 100 days after treatment) received fractionated whole-brain irradiation (one 5 Gy fraction/week for four weeks) with a total dose of 20 Gy of gamma rays. Morris water maze cognitive testing, histochemistry, immunohistochemistry and confocal microscopy were used to determine whether the cognitive changes are associated with the alteration of neurogenesis, astrocytic response and activation of microglia along and/or adjacent to well-defined pathway, subventricular zone-olfactory bulb axis (SVZ-OB axis).
Irradiation revealed altered cognitive functions usually at 100 days after treatment. Neurodegenerative changes were characterized by a significant increase of Fluoro-Jade-positive cells 30 days after irradiation accompanied by a steep decline of neurogenesis 100 days after treatment. A strong astrocytic response and upregulation of the activated microglia were seen in both of experimental groups.
Results shows that fractionated irradiation led to cognitive impairment closely associated with accerelation of neuronal cell death, inhibition of neurogenesis, activation of astrocytes and microglia indicate early delayed radiation-induced changes.
本研究旨在探讨在放射性脑损伤实验模型中，神经源性区域的组织病理学变化是否与相应的认知障碍相关。
成年雄性Wistar大鼠被随机分为假照射组（0 Gy）和两个实验组（治疗后存活30天和100天），接受分次全脑照射（每周1次，每次5 Gy，共4周），总剂量为20 Gy的γ射线。采用Morris水迷宫认知测试、组织化学、免疫组织化学和共聚焦显微镜来确定认知变化是否与沿明确通路、脑室下区-嗅球轴（SVZ-OB轴）及其相邻区域的神经发生改变、星形胶质细胞反应和小胶质细胞激活有关。
照射后通常在治疗100天时出现认知功能改变。神经退行性变化的特征是照射后30天Fluoro-Jade阳性细胞显著增加，同时治疗100天后神经发生急剧下降。在两个实验组中均观察到强烈的星形胶质细胞反应和活化小胶质细胞的上调。
结果表明，分次照射导致认知障碍，这与神经元细胞死亡加速、神经发生抑制、星形胶质细胞和小胶质细胞激活密切相关，提示早期延迟性放射性改变。
