An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model
An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model
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DOI：
10.1002/nbm.980
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发表时间：
2005-12-01
影响因子：
2.9
通讯作者：
Berman, RF
中科院分区：
文献类型：
--
作者：
Viant, MR;Lyeth, BG;Berman, RF
使用脑组织提取物和血浆的高分辨率 H-1 NMR 代谢组学检查了三组大鼠的创伤性脑损伤 (TBI) 对脑化学和代谢的影响。 TBI 组 (n = 6) 的脑损伤是通过侧向液体冲击造成的，并在损伤后 1 小时分析海马、皮质和血浆中脑代谢物的区域变化，并与假手术对照组 (n = 6) 和未经治疗的对照组 (it = 6) 的变化进行比较。有证据表明，与未经治疗的对照组相比，TBI 大鼠存在氧化应激（例如，皮质和海马中的抗坏血酸分别减少了 16.4%（P < 0.01）和 29.7%（p < 0.05）），以及兴奋性毒性损伤（例如，谷氨酸减少了 14.7%（p < 0.05）和 12.3%） （p < 皮层和海马中的磷酸胆碱和甘油磷酸胆碱的总水平分别降低了 23.0% (p < 0.01) 和 19.0% (p < 0.01)）、膜破坏（例如，皮质和海马中的 N-乙酰天冬氨酸水平分别降低）和神经元损伤（例如，神经元损伤） 皮层和海马体中分别为 15.3% (p < 0.01) 和 9.7% (p > 0.05)。在 TBI 动物中，使用主成分分析还观察到 NMR 可观察代谢物总体模式的显着变化。尽管 TBI 明显对脑组织中的代谢谱有影响，但在血浆样本中没有发现明显的影响。这至少部分是由于血浆中主要葡萄糖和乳酸峰的巨大变异性造成的。然而，血脑屏障的破坏以及随后代谢物从大脑转移到血液中的程度可能相对较小，并且低于分析程序的检测限。全面的。这些数据表明，TBI 会导致创伤后早期大脑代谢发生一些显着变化，并且基于 H-1 NMR 光谱的代谢组学方法可以提供包含几种代谢物类别的代谢概况，并允许对特定大脑区域内的此类变化进行相对量化。研究结果还为研究 TBI 的代谢组学技术的进一步开发和应用以及利用多变量模型对个体内创伤程度进行分类提供了支持。版权所有 (c) 2005 John Wiley & Sons, Ltd.
The effects of traumatic brain injury (TBI) on brain chemistry and metabolism were examined in three Groups of rats using high-resolution H-1 NMR metabolomics of brain tissue extracts and plasma. Brain injury in the TBI group (n = 6) was produced by lateral fluid percussion and regional changes in brain metabolites were analyzed at 1 h after injury in hippocampus, cortex and plasma and compared with changes in both a sham-surgery control group (n = 6) and an untreated control group (it = 6). Evidence was found of oxidative stress (e.g. decreases in ascorbate of 16.4% (P < 0.01) and 29.7% (p < 0.05) in cortex and hippocarnpus, respectively) in TBI rats versus the untreated control group, as well as excitotoxic damage (e.g. decreases in glutamate of 14.7% (p < 0.05) and 12.3% (p < 0.01) in the cortex and hippocampus, respectively), membrane disruption (e.g. decreases in the total level of phosphocholine and glycerophosphocholine of 23.0% (p < 0.01) and 19.0% (p < 0.01) in the cortex and hippocarnpus, respectively) and neuronal injury (e.g. decreases in N-acetylaspartate of 15.3% (p < 0.01) and 9.7% (p > 0.05) in the cortex and hippocampus, respectively). Significant changes in the overall pattern of NMR-observable metabolites using principal components analysis were also observed in TBI animals. Although TBI clearly had an effect on the metabolic profile found in brain tissue, no clear effects could be discerned in plasma samples. This was at least partly due to large variability in dominant Glucose and lactate peaks in plasma. However, disruption of the blood-brain barrier and the subsequent movement of metabolites from brain into blood may have been relatively small and below the detection limits of out-analytical procedures. Overall. these data indicate that TBI results in several significant changes in brain metabolism early after trauma and that a metabolomic approach based on H-1 NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes within specific brain regions. The results also provide Support for further development and application of metabolomic technologies for studying TBI and for the utilization of multivariate models for classifying the extent of trauma within an individual. Copyright (c) 2005 John Wiley & Sons, Ltd.