Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 036 01, Martin, Slovak Republic.
Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4D, 036 01, Martin, Slovak Republic.
Neurochem Int. 2021 May;145:104985. doi: 10.1016/j.neuint.2021.104985. Epub 2021 Feb 11.
In the present study, we investigated the correlation between histopathological, metabolic, and volumetric changes in the brain and plasma under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 32 Gy delivered in 4 fractions (dose 8 Gy per fraction) once a week on the same day for 4 consecutive weeks. Proton magnetic resonance spectroscopy (H MRS) and imaging were used to detect metabolic and volumetric changes in the brain and plasma. Histopathological changes in the brain were determined by image analysis of immunofluorescent stained sections. Metabolic changes in the brain measured by H MRS before, 48 h, and 9 weeks after the end of fWBI showed a significant decrease in the ratio of total N-acetylaspartate to total creatine (tNAA/tCr) in the corpus striatum. We found a significant decrease in glutamine + glutamate/tCr (Glx/tCr) and, conversely, an increase in gamma-aminobutyric acid to tCr (GABA/tCr) in olfactory bulb (OB). The ratio of astrocyte marker myoinositol/tCr (mIns/tCr) significantly increased in almost all evaluated areas. Magnetic resonance imaging (MRI)-based brain volumetry showed a significant increase in volume, and a concomitant increase in the T relaxation time of the hippocampus. Proton nuclear magnetic resonance (H NMR) plasma metabolomics displayed a significant decrease in the level of glucose and glycolytic intermediates and an increase in ketone bodies. The histomorphological analysis showed a decrease to elimination of neuroblasts, increased astrocyte proliferation, and a mild microglia response. The results of the study clearly reflect early subacute changes 9-11 weeks after fWBI with strong manifestations of brain edema, astrogliosis, and ongoing ketosis.
在本研究中，我们在实验条件下研究了大脑和血浆的组织病理学、代谢和体积变化之间的相关性。成年雄性 Wistar 大鼠接受 32 Gy 全脑分割照射（fWBI），每周一次，连续 4 周，共 4 个剂量（每个剂量 8 Gy）。质子磁共振波谱（H MRS）和成像用于检测大脑和血浆的代谢和体积变化。通过免疫荧光染色切片的图像分析确定大脑的组织病理学变化。在 fWBI 结束后 48 小时和 9 周之前、期间和之后测量的大脑代谢变化通过 H MRS 显示纹状体中的总 N-乙酰天冬氨酸与总肌酸（tNAA/tCr）比值显著降低。我们发现嗅球（OB）中的谷氨酰胺+谷氨酸/tCr（Glx/tCr）显著降低，相反，γ-氨基丁酸与 tCr（GABA/tCr）比值增加。星形胶质细胞标志物肌醇/tCr（mIns/tCr）的比值在几乎所有评估区域均显著增加。基于磁共振成像（MRI）的脑容量显示体积显著增加，同时海马体 T 弛豫时间增加。质子磁共振（H NMR）血浆代谢组学显示葡萄糖和糖酵解中间产物水平显著降低，酮体增加。组织形态学分析显示神经母细胞减少或消除，星形胶质细胞增殖增加，轻度小胶质细胞反应。研究结果清楚地反映了 fWBI 后 9-11 周的早期亚急性变化，表现为明显的脑水肿、星形胶质细胞增生和持续的酮症。
