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Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2017-08-14 00:00:00 , DOI: 10.1021/acschemneuro.7b00189
Damon C. Barbacci 1 , Aurelie Roux 2 , Ludovic Muller 2 , Shelley N. Jackson 2 , Jeremy Post 2 , Kathrine Baldwin 2 , Barry Hoffer 3 , Carey D. Balaban 4 , J. Albert Schultz 1 , Shawn Gouty 5 , Brian M. Cox 5 , Amina S. Woods 2
Affiliation  

Traumatic brain injury (TBI) is a serious public health problem and the leading cause of death in children and young adults. It also contributes to a substantial number of cases of permanent disability. As lipids make up over 50% of the brain mass and play a key role in both membrane structure and cell signaling, their profile is of particular interest. In this study, we show that advanced mass spectrometry imaging (MSI) has sufficient technical accuracy and reproducibility to demonstrate the anatomical distribution of 50 μm diameter microdomains that show changes in brain ceramide levels in a rat model of controlled cortical impact (CCI) 3 days post injury with and without treatment. Adult male Sprague–Dawley rats received one strike and were euthanized 3 days post trauma. Brain MS images showed increase in ceramides in CCI animals compared to control as well as significant reduction in ceramides in CCI treated animals, demonstrating therapeutic effect of a peptide agonist. The data also suggests the presence of diffuse changes outside of the injured area. These results shed light on the extent of biochemical and structural changes in the brain after traumatic brain injury and could help to evaluate the efficacy of treatments.

中文翻译:

神经酰胺生物标志物的质谱成像可追踪创伤性脑损伤中的治疗反应

颅脑外伤(TBI)是一个严重的公共卫生问题,是儿童和年轻人死亡的主要原因。它还导致大量永久性残疾案件。由于脂质占大脑质量的50%以上,并且在膜结构和细胞信号传导中都起着关键作用,因此,脂质的分布特别受到关注。在这项研究中,我们表明,先进的质谱成像(MSI)具有足够的技术准确性和可重复性,可以证明直径为50μm的微区的解剖分布,在大鼠皮层撞击控制(CCI)3天模型中显示了脑神经酰胺水平的变化。有或没有治疗的受伤后情况。成年雄性Sprague–Dawley大鼠受到一击,并在受伤后3天被安乐死。脑MS图像显示,与对照组相比,CCI动物中神经酰胺含量增加,而在CCI处理过的动物中神经酰胺含量显着降低,这证明了肽激动剂的治疗作用。数据还表明在受伤区域之外存在弥散变化。这些结果揭示了脑外伤后脑中生化和结构变化的程度,可以帮助评估治疗的有效性。
更新日期:2017-08-14
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