Department of Anesthesiology, Health Sciences Center, Stony Brook University, Stony Brook, New York 11794, USA.
J Cereb Blood Flow Metab. 2011 Jun;31(6):1432-42. doi: 10.1038/jcbfm.2011.1. Epub 2011 Jan 26.
Development of noninvasive techniques to discover new biomarkers in the live brain is important to further understand the underlying metabolic pathways of significance for processes such as anesthesia-induced apoptosis and cognitive dysfunction observed in the undeveloped brain. We used in vivo proton magnetic resonance spectroscopy and two different signal processing approaches to test the hypothesis that volatile (isoflurane) and intravenous (propofol) anesthetics at equipotent doses produce distinct metabolomic profiles in the hippocampus and parietal cortex of the live rodent. For both brain regions, prolonged isoflurane anesthesia was characterized by higher levels of lactate (Lac) and glutamate compared with long-lasting propofol. In contrast, propofol anesthesia was characterized by very low concentrations of Lac ([lac]) as well as glucose. Quantitative analysis revealed that the [lac] was fivefold higher with isoflurane compared with propofol anesthesia and independent of [lac] in blood. The metabolomic profiling further demonstrated that for both brain regions, Lac was the most important metabolite for the observed differences, suggesting activation of distinct metabolic pathways that may impact mechanisms of action, background cellular functions, and possible agent-specific neurotoxicity.
开发非侵入性技术以在活体大脑中发现新的生物标志物对于进一步理解麻醉诱导的细胞凋亡和认知功能障碍等过程的潜在代谢途径非常重要，这些现象在未成熟的大脑中观察到。我们使用体内质子磁共振波谱和两种不同的信号处理方法来检验以下假设：在等效剂量下，挥发性（异氟烷）和静脉内（异丙酚）麻醉剂会在活体啮齿动物的海马体和顶叶皮层产生不同的代谢组学特征。对于这两个脑区，与长时间的异丙酚相比，长时间的异氟烷麻醉会导致更高水平的乳酸（Lac）和谷氨酸。相比之下，异丙酚麻醉的特点是 Lac（[Lac]）浓度非常低，同时葡萄糖浓度也很低。定量分析显示，与异丙酚麻醉相比，异氟烷麻醉时的 Lac 水平高五倍，且与血液中的 Lac 水平无关。代谢组学分析进一步表明，对于这两个脑区，Lac 是观察到的差异的最重要代谢物，这表明激活了不同的代谢途径，可能会影响作用机制、背景细胞功能和可能的特定药物神经毒性。
