, 15:152 | Cite as

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

  • Chaofu Ke
  • Chen-Wei Pan
  • Yuxia Zhang
  • Xiaohong Zhu
  • Yonghong ZhangEmail author
Review Article



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.


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.


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.


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.


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.


Ischemic stroke Metabolomics Biomarker Metabolic pathway Pathogenesis 



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


Branched chain amino acid


Disability-adjusted life year


Intracerebral hemorrhage




Ischemic stroke




Nuclear magnetic resonance




Large-artery atherosclerosis




Phospholipase A2


Post-stroke cognition impairment


Post-stroke depression


Trimethylamine N-oxide



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 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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11306_2019_1615_MOESM1_ESM.doc (174 kb)
Supplementary material 1 (DOC 174 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Chaofu Ke
    • 1
  • Chen-Wei Pan
    • 2
  • Yuxia Zhang
    • 1
  • Xiaohong Zhu
    • 3
  • Yonghong Zhang
    • 1
    Email author
  1. 1.Department of Epidemiology and Biostatistics, School of Public HealthMedical College of Soochow UniversitySuzhouPeople’s Republic of China
  2. 2.School of Public HealthMedical College of Soochow UniversitySuzhouChina
  3. 3.Suzhou Industrial Park Centers for Disease Control and Prevention (Institute of Health Inspection and Supervision)SuzhouPeople’s Republic of China

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