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A Metabolomics Study of Hypoxia Ischemia during Mouse Brain Development Using Hyperpolarized 13C.
Developmental Neuroscience ( IF 2.9 ) Pub Date : 2020-06-22 , DOI: 10.1159/000506982
Alkisti Mikrogeorgiou 1 , Yiran Chen 2, 3 , Byong Sop Lee 4 , Robert Bok 2 , R Ann Sheldon 1 , A James Barkovich 2, 5 , Duan Xu 6, 7 , Donna M Ferriero 1
Affiliation  

Background: Hyperpolarized 13C spectroscopic magnetic resonance spectroscopy (MRS) is an advanced imaging tool that may provide important real-time information about brain metabolism. Methods: Mice underwent unilateral hypoxia-ischemia (HI) on postnatal day (P)10. Injured and sham mice were scanned at P10, P17, and P31. We used hyperpolarized 13C MRS to investigate the metabolic exchange of pyruvate to lactate in real time during brain development following HI. 13C-1-labeled pyruvate was hyperpolarized and injected into the tail vein through a tail-vein catheter. Chemical-shift imaging was performed to acquire spectral-spatial information of the metabolites in the brain. A voxel placed on each of the injured and contralateral hemispheres was chosen for comparison. The difference in pyruvate delivery and lactate to pyruvate ratio was calculated for each of the voxels at each time point. The normalized lactate level of the injured hemisphere was also calculated for each mouse at each of the scanning time points. Results: There was a significant reduction in pyruvate delivery and a higher lactate to pyruvate ratio in the ipsilateral (HI) hemisphere at P10. The differences decreased at P17 and disappeared at P31. The normalized lactate level in the injured hemisphere increased from P10 to P31 in both sham and HI mice without brain injury. Conclusion: We describe a method for detecting and monitoring the evolution of HI injury during brain maturation which could prove to be an excellent biomarker of injury.
Dev Neurosci


中文翻译:

使用超极化 13C 对小鼠大脑发育过程中缺氧缺血的代谢组学研究。

背景:超极化13 C 光谱磁共振波谱 (MRS) 是一种先进的成像工具,可以提供有关大脑代谢的重要实时信息。方法:小鼠在出生后第 10 天(P)接受单侧缺氧缺血(HI)。在 P10、P17 和 P31 扫描受伤和假小鼠。我们使用超极化13 C MRS 来实时研究 HI 后大脑发育过程中丙酮酸到乳酸的代谢交换。13C-1 标记的丙酮酸被超极化并通过尾静脉导管注入尾静脉。进行化学位移成像以获取大脑中代谢物的光谱空间信息。选择放置在每个受伤半球和对侧半球上的体素进行比较。在每个时间点计算每个体素的丙酮酸递送和乳酸与丙酮酸比率的差异。在每个扫描时间点,还计算了每只小鼠受伤半球的标准化乳酸水平。结果:在 P10 时,同侧 (HI) 半球的丙酮酸递送显着减少,乳酸与丙酮酸的比率更高。差异在 P17 时减少,在 P31 时消失。在没有脑损伤的假手术和 HI 小鼠中,受伤半球的标准化乳酸水平从 P10 增加到 P31。结论:我们描述了一种用于检测和监测脑成熟过程中 HI 损伤演变的方法,该方法可以证明是一种极好的损伤生物标志物。
开发神经科学
更新日期:2020-06-23
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