Brain development is an energy-expensive process. Although glucose is irreplaceable, the developing brain utilizes a variety of substrates such as lactate and the ketone bodies, β-hydroxybutyrate and acetoacetate, to produce energy and synthesize the structural components necessary for cerebral maturation. When oxygen and nutrient supplies to the brain are restricted, as in neonatal hypoxia-ischemia (HI), cerebral energy metabolism undergoes alterations in substrate use to preserve the production of adenosine triphosphate. These changes have been studied by in situ biochemical methods that yielded valuable quantitative information about high-energy and glycolytic metabolites and established a temporal profile of the cerebral metabolic response to hypoxia and HI. However, these analyses relied on terminal experiments and averaging values from several animals at each time point as well as challenging requirements for accurate tissue processing.More recent methodologies have focused on in vivo longitudinal analyses in individual animals. The emerging field of metabolomics provides a new investigative tool for studying cerebral metabolism. Magnetic resonance spectroscopy (MRS) has enabled the acquisition of a snapshot of the metabolic status of the brain as quantifiable spectra of various intracellular metabolites. Proton (1H) MRS has been used extensively as an experimental and diagnostic tool of HI in the pursuit of markers of long-term neurodevelopmental outcomes. Still, the interpretation of the metabolite spectra acquired with 1H MRS has proven challenging, due to discrepancies among studies, regarding calculations and timing of measurements. As a result, the predictive utility of such studies is not clear. 13C MRS is methodologically more challenging, but it provides a unique window on living tissue metabolism via measurements of the incorporation of 13C label from substrates into brain metabolites and the localized determination of various metabolic fluxes. The newly developed hyperpolarized 13C MRS is an exciting method for assessing cerebral metabolism in vivo, that bears the advantages of conventional 13C MRS but with a huge gain in signal intensity and much shorter acquisition times. The first part of this review article provides a brief description of the findings of biochemical and imaging methods over the years as well as a discussion of their associated strengths and pitfalls. The second part summarizes the current knowledge on cerebral metabolism during development and HI brain injury.

中文翻译：

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评估未成熟啮齿动物的脑代谢：从提取物到实时评估。

大脑发育是一个耗能的过程。尽管葡萄糖是不可替代的，但发育中的大脑利用了多种底物，例如乳酸和酮体，β-羟基丁酸酯和乙酰乙酸酯，来产生能量并合成大脑成熟所需的结构成分。如新生儿缺氧缺血（HI）一样，当限制向大脑提供氧气和营养时，脑能量代谢会发生底物用途的变化，从而保持三磷酸腺苷的生成。这些变化已经通过原位生化方法进行了研究，这些方法产生了有关高能和糖酵解代谢物的有价值的定量信息，并建立了对低氧和HI的脑代谢反应的时间分布。然而，这些分析依赖于最终实验以及每个时间点上几只动物的平均值以及对精确组织处理的挑战性要求。最近的方法学已集中在单个动物的体内纵向分析上。代谢组学的新兴领域为研究脑代谢提供了一种新的研究工具。磁共振波谱（MRS）使人们能够获取大脑代谢状态的快照，作为各种细胞内代谢产物的可量化谱。质子（1H）MRS已广泛用作HI的实验和诊断工具，以寻求长期神经发育结局的标志物。尽管如此，由于研究之间的差异，使用1H MRS采集的代谢物光谱的解释已被证明具有挑战性，关于计算和测量时间。结果，此类研究的预测效用尚不清楚。13C MRS在方法上更具挑战性，但是它通过测量从底物到大脑代谢物中的13C标记掺入以及各种代谢通量的局部测定，为活组织代谢提供了一个独特的窗口。新开发的超极化13C MRS是一种评估体内脑代谢的令人兴奋的方法，它具有常规13C MRS的优点，但信号强度大大提高，采集时间大大缩短。这篇综述文章的第一部分简要介绍了多年来生物化学和成像方法的发现，并讨论了它们的相关优势和缺陷。