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通过扩散张量成像评估一种神经调节药物的微观结构效应。

Microstructural effects of a neuro-modulating drug evaluated by diffusion tensor imaging.

作者信息

Egger K, Janz P, Döbrössy M D, Bienert T, Reisert M, Obmann M, Glauche V, Haas C, Harsan L A, Urbach H, von Elverfeldt D

机构信息

Department of Neuroradiology, University Medical Center Freiburg, Germany.

Experimental Epilepsy Research, Department of Neurosurgery, University Medical Center Freiburg, Germany.

出版信息

Neuroimage. 2016 Feb 15;127:1-10. doi: 10.1016/j.neuroimage.2015.10.091. Epub 2015 Dec 2.

Abstract

In a longitudinal mouse study we evaluated whether diffusion tensor imaging (DTI) can monitor microstructural changes after administration of the neuromodulating drug EPO and whether erythropoietin (EPO) has an effect on cognitive performance. Twelve mice (2 groups with 6 mice each) were scanned in a 7T Bruker Biospin animal scanner with a highly resolved DTI sequence before and 16 days after intraperitoneal injections of EPO or saline. All mice underwent behavioral testing (Morris water maze) and histologic evaluation of hippocampal and corpus callosum cell proliferation and oligodendrogenesis. Whole brain DTI analysis showed significant Trace, RD and AD decrease within the dentate gyrus, subiculum, primary motor, somatosensory, and supplementary somatosensory areas and FA increase in the hippocampus, corpus callosum, and fimbria fornix in EPO treated mice only. ROI-based DTI analysis showed significant Trace and RD decrease and FA increase only in the corpus callosum of EPO treated mice, whereas in the dentate gyrus significant Trace, RD, and AD decrease occurred in both, EPO- and control-group. Behavioral tests showed that EPO treated mice performed better and learned faster than controls. Histologically, the number of BrdU-positive nuclei and optical density of DCX-labeled juvenile neurons significantly increased within the dentate gyrus, corpus callosum and fimbria fornix and the number of NG2-positive oligodendrocyte progenitors in corpus callosum and fimbria fornix, respectively. In conclusion we were able to monitor microstructural changes with DTI and showed EPO treatment-related alterations correlating with enhanced dentate gyrus and corpus callosum cell proliferation and better learning capabilities.

摘要

在一项纵向小鼠研究中,我们评估了扩散张量成像(DTI)能否监测神经调节药物促红细胞生成素(EPO)给药后的微观结构变化,以及促红细胞生成素(EPO)是否对认知能力有影响。将12只小鼠(分为2组,每组6只)在7T布鲁克生物自旋动物扫描仪中,使用高分辨率DTI序列在腹腔注射EPO或生理盐水之前和之后16天进行扫描。所有小鼠均接受行为测试(莫里斯水迷宫)以及海马体和胼胝体细胞增殖和少突胶质细胞生成的组织学评估。全脑DTI分析显示,仅在EPO处理的小鼠中,齿状回、海马下托、初级运动区、躯体感觉区和辅助躯体感觉区内的迹值、径向扩散(RD)和轴向扩散(AD)显著降低,而海马体、胼胝体和穹窿系带中的分数各向异性(FA)增加。基于感兴趣区(ROI)的DTI分析显示,仅在EPO处理的小鼠的胼胝体中,迹值和RD显著降低,FA增加,而在齿状回中,EPO组和对照组的迹值、RD和AD均显著降低。行为测试表明,EPO处理的小鼠比对照组表现更好,学习速度更快。组织学上,齿状回、胼胝体和穹窿系带内BrdU阳性细胞核的数量以及DCX标记的幼年神经元的光密度显著增加,胼胝体和穹窿系带中NG2阳性少突胶质细胞祖细胞的数量也分别显著增加。总之,我们能够用DTI监测微观结构变化,并表明EPO治疗相关的改变与齿状回和胼胝体细胞增殖增强以及更好的学习能力相关。

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