Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury.
Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury.
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DOI：
10.1021/acschemneuro.7b00189
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发表时间：
2017-10-18
影响因子：
5
通讯作者：
Woods AS
中科院分区：
文献类型：
--
作者：
Barbacci DC;Roux A;Muller L;Jackson SN;Post J;Baldwin K;Hoffer B;Balaban CD;Schultz JA;Gouty S;Cox BM;Woods AS
创伤性脑损伤（TBI）是一个严重的公共卫生问题，也是儿童和年轻人死亡的主要原因。这也是造成大量永久残疾的原因之一。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起着关键作用，因此它们的分布特别令人感兴趣。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再现性，以证明50 μm直径的微区的解剖分布，显示脑神经酰胺水平的变化，在大鼠模型的控制性皮质撞击（CCI）损伤后3天，治疗和不治疗。成年雄性Sprague-Dawley大鼠接受一次攻击，并在创伤后3天安乐死。脑MS图像显示与对照相比CCI动物中神经酰胺的增加以及CCI处理的动物中神经酰胺的显著减少，证明肽激动剂的治疗效果。数据还表明，在受伤区域之外存在弥漫性变化。这些结果揭示了创伤性脑损伤后脑内生化和结构变化的程度，并有助于评估治疗的疗效。
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.
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