Integration of 1H NMR- and UPLC-Q-TOF/MS-based plasma metabonomics study to identify diffuse axonal injury biomarkers in rat

Zhang, Peng; Zhu, Shisheng; Zhao, Min; Dai, Yalei; Zhang, Li; Ding, Shijia; Zhao, Peng; Li, Jianbo

doi:10.1016/j.brainresbull.2018.03.012

Cited by 18 publications

(19 citation statements)

References 41 publications

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“…MRS exploits metabolic alterations in neurodegenerative diseases and brain tumors [42][43][44][45], but evidence following mTBI is sparse. Animal studies using MRS after experimental TBI suggest Gln, pyruvate, glycerol, and phosphocholine as suitable metabolites to detect diffuse axonal injury and posttraumatic neurodegeneration [46][47][48][49][50]. However, patients with early signs of dementia have exhibited reductions in Glu and NAA [51], suggesting that these metabolic alterations are not specific for TBI, but might point to the posttraumatic pathway and link to neurodegeneration.…”

Section: Mrs and The Link To Neurodegenerationmentioning

confidence: 99%

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Eisele¹,

Hill-Strathy²,

Michels³

et al. 2020

Neurodegener Dis

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Introduction: Traumatic brain injury (TBI) is the most relevant external risk factor for dementia and a major global health burden. Mild TBI (mTBI) contributes to up to 90% of all TBIs, and the classification “mild” often misrepresents the patient’s burden who suffer from neuropsychiatric long-term sequelae. Magnetic resonance spectroscopy (MRS) allows in vivo detection of compromised brain metabolism although it is not routinely used after TBI. Objective: Thus, we performed a systematic review and meta-analysis to elucidate if MRS has the potential to identify changes in brain metabolism in adult patients after a single mTBI with a negative routine brain scan (CCT and/or MRI scan) compared to aged- and sex-matched healthy controls (HC) during the acute or subacute postinjury phase (≤90 days after mTBI). Methods: A comprehensive literature search was conducted from the first edition of electronic databases until January 31, 2020. Group analyses were performed per metabolite using a random-effects model. Results: Four and 2 out of 5,417 articles met the inclusion criteria for the meta-analysis and systematic review, respectively. For the meta-analysis, 50 mTBI patients and 51 HC with a mean age of 31 and 30 years, respectively, were scanned using N-acetyl-aspartate (NAA), a marker for neuronal integrity. Glutamate (Glu), a marker for disturbed brain metabolism, choline (Cho), a marker for increased cell membrane turnover, and creatine (Cr) were used in 2 out of the 4 included articles. Regions of interests were the frontal lobe, the white matter around 1 cm above the lateral ventricles, or the whole brain. NAA was decreased in patients compared to HC with an effect size (ES) of –0.49 (95% CI –1.08 to 0.09), primarily measured in the frontal lobe. Glu was increased in the white matter in 22 mTBI patients compared to 22 HC (ES 0.79; 95% CI 0.17–1.41). Cho was decreased in 31 mTBI patients compared to 31 HC (ES –0.31; 95% CI –0.81 to 0.19). Cr was contradictory and, therefore, potentially not suitable as a reference marker after mTBI. Conclusions: MRS pinpoints changes in posttraumatic brain metabolism that correlate with cognitive dysfunction and, thus, might possibly help to detect mTBI patients at risk for unfavorable outcome or posttraumatic neurodegeneration early.

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Section: Mrs and The Link To Neurodegenerationmentioning

confidence: 99%

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Eisele¹,

Hill-Strathy²,

Michels³

et al. 2020

Neurodegener Dis

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“…Due to the own features of MS and NMR, a distinct set of metabolites from the same sample tend to be observed. Therefore, tandem studies have become popular to analyze the same sample with MS and NMR (Bingol and Bruschweiler, ; Gathungu et al, ; Zhang et al, ). In this way, the coverage of metabolites can be proportional increased by taking advantage of the two methods.…”

Section: Metabolomics: An Overviewmentioning

confidence: 99%

Novel applications of mass spectrometry‐based metabolomics in herbal medicines and its active ingredients: Current evidence

Wang

Ren

Zhang

et al. 2019

Mass Spectrometry Reviews

103

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Current evidence shows that herbal medicines could be beneficial for the treatment of various diseases. However, the complexities present in chemical compositions of herbal medicines are currently an obstacle for the progression of herbal medicines, which involve unclear bioactive compounds, mechanisms of action, undetermined targets for therapy, non‐specific features for drug metabolism, etc. To overcome those issues, metabolomics can be a great to improve and understand herbal medicines from the small‐molecule metabolism level. Metabolomics could solve scientific difficulties with herbal medicines from a metabolic perspective, and promote drug discovery and development. In recent years, mass spectrometry‐based metabolomics was widely applied for the analysis of herbal constituents in vivo and in vitro. In this review, we highlight the value of mass spectrometry‐based metabolomics and metabolism to address the complexity of herbal medicines in systems pharmacology, and to enhance their biomedical value in biomedicine, to shed light on the aid that mass spectrometry‐based metabolomics can offer to the investigation of its active ingredients, especially, to link phytochemical analysis with the assessment of pharmacological effect and therapeutic potential. © 2019 Wiley Periodicals, Inc. Mass Spec Rev

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“…The underlying pathophysiological mechanisms of widespread axonal injury in DAI are quite complex and remain largely unclear [5]. Recent studies have demonstrated that DAI is a multi-stage biological process disorder with substantial molecular alterations and pathway dysregulations involved [5,6,7]. At present, there are still no objective and reliable biomarkers for clinicians to enable early diagnosis of DAI, which results in a high rate of underdiagnosis and an increased disability and mortality risk [8,9].…”

Section: Introductionmentioning

confidence: 99%

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

Song

Zhu

Zhang

et al. 2019

IJMS

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Diffuse axonal injury (DAI) is a prevalent and serious brain injury with significant morbidity and disability. However, the underlying pathogenesis of DAI remains largely unclear, and there are still no objective laboratory-based tests available for clinicians to make an early diagnosis of DAI. An integrated analysis of metabolomic data and proteomic data may be useful to identify all of the molecular mechanisms of DAI and novel potential biomarkers. Therefore, we established a rat model of DAI, and applied an integrated UPLC-Q-TOF/MS-based metabolomics and isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to obtain unbiased profiling data. Differential analysis identified 34 metabolites and 43 proteins in rat plasma of the injury group. Two metabolites (acetone and 4-Hydroxybenzaldehyde) and two proteins (Alpha-1-antiproteinase and Alpha-1-acid glycoprotein) were identified as potential biomarkers for DAI, and all may play important roles in the pathogenesis of DAI. Our study demonstrated the feasibility of integrated metabolomics and proteomics method to uncover the underlying molecular mechanisms of DAI, and may help provide clinicians with some novel diagnostic biomarkers and therapeutic targets.

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Integration of 1H NMR- and UPLC-Q-TOF/MS-based plasma metabonomics study to identify diffuse axonal injury biomarkers in rat

Cited by 18 publications

References 41 publications

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Magnetic Resonance Spectroscopy following Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis on the Potential to Detect Posttraumatic Neurodegeneration

Novel applications of mass spectrometry‐based metabolomics in herbal medicines and its active ingredients: Current evidence

Integrated Proteomics and Metabolomic Analyses of Plasma Injury Biomarkers in a Serious Brain Trauma Model in Rats

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