Metabolomics in Ischemic Stroke Research

Ischaemic stroke arises from interrupted cerebral blood flow leading to energy failure and neuronal death. Metabolomics, the comprehensive study of small molecules in biological systems, offers direct insight into the biochemical perturbations underpinning this insult. By profiling metabolites in biofluids, tissue or cerebrospinal fluid, researchers can detect signatures of excitotoxicity, oxidative stress, inflammation and blood–brain barrier disruption. Advances in high-resolution mass spectrometry and nuclear magnetic resonance have greatly enhanced sensitivity, allowing the dynamic measurement of amino acids, lipids, nucleotides and intermediary metabolites. Integration with genomic, proteomic and imaging data has clarified distinct metabolic pathways activated during the acute phase, reperfusion and recovery. Clinically, metabolomic biomarkers hold promise for early diagnosis, prognosis and stratification of subtypes, while mechanistic studies in animal models have identified targets for neuroprotection, such as metabolic enzymes driving reactive oxygen species and endothelial pyroptosis. Global collaborations have enriched sample diversity, revealing how age, co-morbidities and ethnic background shape metabolic responses. Despite challenges in standardisation and data analysis, ongoing refinement of analytical platforms and bioinformatics pipelines is accelerating translation into precision medicine. Future directions include longitudinal studies to monitor recovery, point-of-care assays for rapid bedside testing and combining metabolomics with emerging modalities such as single-cell metabolite imaging to map spatial microenvironmental changes. This expanding toolkit positions metabolomics at the forefront of efforts to mitigate the burden of ischaemic stroke worldwide.

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Metabolomics in Ischemic Stroke Research publication trend

The graph below shows the total number of articles in metabolomics in ischemic stroke research across all publications each year (not limited to Nature Index journals).

Technical terms

Metabolomics: The systematic study of small molecules and metabolic pathways within cells, tissues or organisms.

Ischaemic stroke: A type of stroke caused by the obstruction of cerebral blood flow, resulting in brain tissue hypoxia.

Reperfusion injury: Tissue damage caused when blood supply returns to the tissue after a period of ischaemia.

Blood–brain barrier (BBB): A selective endothelial interface that regulates movement of molecules between the bloodstream and the brain.

Pyroptosis: A form of programmed cell death associated with inflammation and mediated by membrane pore-forming proteins.

Succinate dehydrogenase (SDH): A mitochondrial enzyme complex that oxidises succinate to fumarate and contributes to electron transport.

Mass spectrometry (MS): An analytical technique for identifying and quantifying molecules by their mass-to-charge ratio.

References

1. Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke. Theranostics (2024).
2. Targeting succinate metabolism to decrease brain injury upon mechanical thrombectomy treatment of ischemic stroke. Redox Biology (2023).
3. Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke. Biomarker Research (2024).