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Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review

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Abstract

Introduction

Ischemic stroke (IS) is a major contributor to the global disease burden, and effective biomarkers for IS management in clinical practice are urgently needed. Metabolomics can detect metabolites that are small enough to cross the blood–brain barrier in a high-throughput manner, and thus represents a powerful tool for discovering biomarkers of IS.

Objectives

In this study, we conducted a systematic review to identify potential metabolic biomarkers and pathways that might facilitate risk predictions, clinical diagnoses, the recognition of complications, predictions of recurrence and an understanding of the pathogenesis of IS.

Methods

The PubMed and Web of Science databases were searched for relevant studies published between January 2000 and July 2019. The study objectives, study designs and reported metabolic biomarkers were systematically examined and compared. Pathway analysis was performed using the MetaboAnalyst online software.

Results

Twenty-eight studies were included in this systematic review. Many consistent metabolites, including isoleucine, leucine, valine, glycine, lysine, glutamate, LysoPC(16:0), LysoPC(18:2), serine, uric acid, citrate and palmitic acid, possess potential as biomarkers of IS. Metabolic pathways and dysregulations that are implicated in excitotoxicity, inflammation, apoptosis, oxidative stress, neuroprotection, energy failure, and elevation of intracellular Ca2+ levels, were indicated as playing important roles in the development and progression of IS.

Conclusions

This systematic review summarizes potential metabolic biomarkers and pathways related to IS, which may provide opportunities for the construction of diagnostic or predictive models for IS and the discovery of novel therapeutic targets.

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Abbreviations

ABCD2:

Age, blood pressure, clinical features, duration of symptoms, and diabetes scale

BCAA:

Branched chain amino acid

DALY:

Disability-adjusted life year

ICH:

Intracerebral hemorrhage

IDO:

Indoleamine-2,3-dioxygenase

IS:

Ischemic stroke

NMDA:

N-methyl-D-aspartate

NMR:

Nuclear magnetic resonance

LPC:

Lysophosphatidylcholine

LAA:

Large-artery atherosclerosis

PC:

Phosphatidylcholine

PLA2:

Phospholipase A2

PSCI:

Post-stroke cognition impairment

PSD:

Post-stroke depression

TMAO:

Trimethylamine N-oxide

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Acknowledgements

This work was funded by the National Natural Science Foundation of China (Project Number 81703316), Natural Science Foundation of Jiangsu Province (Project Number BK20170350) and China Postdoctoral Science Foundation (Project Number 2017M610353).

Author information

Author notes

  1. Chaofu Ke and Chen-Wei Pan made equal contributions to this work.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou, 215123, People’s Republic of China

    Chaofu Ke, Yuxia Zhang & Yonghong Zhang

  2. School of Public Health, Medical College of Soochow University, Suzhou, 215123, China

    Chen-Wei Pan

  3. Suzhou Industrial Park Centers for Disease Control and Prevention (Institute of Health Inspection and Supervision), Suzhou, 215021, Jiangsu, People’s Republic of China

    Xiaohong Zhu

Authors
  1. Chaofu Ke
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  2. Chen-Wei Pan
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  3. Yuxia Zhang
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  4. Xiaohong Zhu
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  5. Yonghong Zhang
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Contributions

YZ and CK conceived and designed the research; CP and CK wrote the manuscript; and CK and YZ performed the data analysis. All authors contributed to the interpretations of the findings. All authors reviewed the manuscript.

Corresponding author

Correspondence to Yonghong Zhang.

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Ke, C., Pan, CW., Zhang, Y. et al. Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review. Metabolomics 15, 152 (2019). https://doi.org/10.1007/s11306-019-1615-1

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