Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method to identify potential biomarkers of perinatal asphyxia in a non-human primate model

Beckstrom, Andrew C.; Humston, Elizabeth M.; Snyder, L.R.; Synovec, Robert E.; Juul, Sandra E.

doi:10.1016/j.chroma.2011.01.086

Cited by 84 publications

(75 citation statements)

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“…This may also reflect the body’s transition from more anaerobic metabolism with less oxygen available to predominantly aerobic metabolism utilizing the TCA cycle. In our previous study on the discovery of biomarkers of perinatal asphyxia (24), two intermediates of the TCA cycle were isolated: succinic acid and malic acid. In that study, these two intermediates showed dramatic elevation following birth and asphyxia, which was thought to be a result of an interruption of the redox reaction with nicotinamide adenine dinucleotide/flavin adenine dinucleotide due to the hypoxia insult.…”

Section: Discussionmentioning

confidence: 99%

“…We recently reported the use of GC × GC–TOFMS in conjunction with innovative chemometric data analysis tools to characterize the metabolic effects of birth asphyxia in a nonhuman primate model (24). We now describe the biochemical changes that occur as nonhuman primates transition to extrauterine life in the absence of experimental asphyxia.…”

Section: Introductionmentioning

confidence: 99%

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The perinatal transition of the circulating metabolome in a nonhuman primate

et al. 2012

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INTRODUCTION The fetal-to-neonatal transition is one of the most complex processes in biological existence; much is unknown about this transition on the molecular and biochemical level. Based on growing metabolomics literature, we hypothesize that metabolomic analysis will reveal the key biochemical intermediates that change during the birth transition. RESULTS Using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC–TOFMS), we identified 100 metabolites that changed during this transition. Of these 100 metabolites, 23 demonstrated significant change during the first 72 h. Of note, four intermediates of the tricarboxylic acid (TCA) cycle were identified (α-ketoglutaric acid, fumaric acid, malic acid, and succinyl-CoA), demonstrating a consistent rate of rise during the study. This may signify the transition of the neonate from a hypoxic in utero environment to an oxygen-rich environment. Important signaling molecules were also identified, including myo-inositol and glutamic acid. DISCUSSION GC × GC–TOFMS was able to identify important metabolites associated with metabolism and signaling. These data can be used as a baseline for normal birth transition, which may aid in future perinatal research investigations. METHODS Late-preterm Macaca nemestrina were delivered by hysterotomy, with plasma drawn from the cord blood and after birth at eight additional time points to 72 h of age.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The perinatal transition of the circulating metabolome in a nonhuman primate

et al. 2012

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“…Fisher ratio analysis is very useful to identify the major compounds responsible for the differences between 2 classes, especially, for example, in the case of on/off responses to illnesses [49]. However, it gives no information regarding changes in the concentration of the analytes present in several classes.…”

Section: Statistical Comparison Using Pairwise Fisher Ratiomentioning

confidence: 99%

Multivariate analysis of mainstream tobacco smoke particulate phase by headspace solid-phase micro extraction coupled with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry

Brokl

Bishop

Wright

et al. 2014

Journal of Chromatography A

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A method involving headspace solid-phase microextraction (HS-SPME) and comprehensive two-dimensional gas chromatography (GC×GC) coupled to time-of-flight mass spectrometry (TOFMS) was developed and applied to evaluate profiles of volatile compounds present in mainstream tobacco smoke particulate matter trapped on glass fiber filters. Six SPME fibers were tested for the extraction capacities toward selected compounds, showing the best results for the polyacrylate fiber. The optimization of the extraction conditions was carried out using multivariate response surface methodology. Two cigarette types differing in a filter design were analyzed using optimized conditions. A template was built in order to generate comprehensive chemical information, which conceded obtaining consistent information across 24 chromatograms. Principal component analysis (PCA) allowed a clear differentiation of the studied cigarette types. Fisher ratio analysis allowed identification of compounds responsible for the chemical differences between the cigarette samples. Of the selected 143 most important ones, 134 analytes were reduced by the active carbon filter, while for nine, classical cellulose acetate filter was more efficient.

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“…Fluid-based metabolomics is an increasingly popular area of research in perinatal medicine, with studies related to neonatal encephalopathy and chorioamnionitis [26,[50][51][52] . Attempts have even been made to correlate metabolic changes with neuropathology in a sheep model of inflammation-driven perinatal brain injury [53] .…”

Section: Time-series Analysismentioning

confidence: 99%

Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

Blaise

Schwendimann

Chhor³

et al. 2017

Dev Neurosci

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Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leading to deficits in learning, memory, and social integration that persist into adulthood. Understanding the underlying processes of the acute effects of excitotoxicity and its persistence during brain maturation provides an opportunity to identify mechanistic or diagnostic biomarkers, thus enabling and designing possible therapies. We applied mass spectrometry to provide metabolic profiles of brain tissue and plasma over time following an excitotoxic lesion (intracerebral ibotenate) to the neonatal (postnatal day 5) mouse brain. We found no differences between the plasma from the control (PBS-injected) and excitotoxic (ibotenate-injected) groups over time (on postnatal days 8, 9, 10, and 30). In the brain, we found that variations in amino acids (arginine, glutamine, phenylananine, and proline) and glycerophospholipids were sustaining acute and delayed (tertiary) responses to injury. In particular, the effect of the excitotoxic lesion on the normal profile of development was linked to alterations in a fingerprint of glycerophospolipids and amino acids. Specifically, we identified increases in the amino acids glutamine, proline, serine, threonine, tryptophan, valine, and the sphingolipid SM C26:1, and decreases in the glycerophospholipids, i.e., the arachidonic acid-containing phosphatidylcholine (PC aa) C30:2 and the PC aa C32:3. This study demonstrates that metabolic profiling is a useful approach to identify acute and tertiary effects in an excitotoxic lesion model, and generating a short list of targets with future potential in the hunt for identification, stratification, and possibly therapy.

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Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method to identify potential biomarkers of perinatal asphyxia in a non-human primate model

Cited by 84 publications

References 47 publications

The perinatal transition of the circulating metabolome in a nonhuman primate

The perinatal transition of the circulating metabolome in a nonhuman primate

Multivariate analysis of mainstream tobacco smoke particulate phase by headspace solid-phase micro extraction coupled with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry

Persistently Altered Metabolic Phenotype following Perinatal Excitotoxic Brain Injury

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