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The metabolomic profile during isoflurane anesthesia differs from propofol anesthesia in the live rodent brain

机译:异氟醚麻醉过程中异氟醚麻醉过程中的代谢组谱与异丙酚麻醉不同。

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摘要

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.
机译:开发非侵入性技术以在活脑中发现新的生物标志物对于进一步了解潜在的代谢途径具有重要意义,这些过程对诸如麻醉诱导的细胞凋亡和未发育的脑中观察到的认知功能障碍等过程具有重要意义。我们使用了体内质子磁共振波谱法和两种不同的信号处理方法来测试以下假设:等势剂量的挥发性(异氟烷)和静脉内(丙泊酚)麻醉剂在活啮齿动物的海马和顶叶皮层产生不同的代谢组学特征。对于两个大脑区域,异氟烷麻醉时间延长的特征是与丙泊酚持续时间相比,乳酸(Lac)和谷氨酸水平更高。相反,丙泊酚麻醉的特征在于Lac([lac])和葡萄糖的浓度非常低。定量分析表明,与异丙酚麻醉相比,异氟烷的[lac]高五倍,并且与血液中的[lac]无关。代谢组学分析进一步表明,对于两个大脑区域来说,Lac是观察到的差异的最重要的代谢产物,表明激活了可能影响作用机制,背景细胞功能以及可能的药物特异性神经毒性的独特代谢途径。

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