Metabolomics facilitates the discovery of metabolic biomarkers and pathways for ischemic stroke: a systematic review
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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.
KeywordsIschemic 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
Nuclear magnetic resonance
Post-stroke cognition impairment
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).
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.
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