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Brain & Heart Cerebral ischemia biomarkers
stratification, treatment monitoring, and prognosis of Metabolomic profiling has shown great promise in
patients with ischemic stroke. identifying biomarkers that can aid in the diagnosis and
Metabolomics analyzes the dynamic changes of small prognosis of cerebral ischemia. The identified metabolites
molecules involved in cellular processes. Metabolomic shed light on the underlying metabolic dysregulations
profiling in cerebral ischemia has revealed altered that occur during ischemic stroke, highlighting different
concentrations of various metabolites, including amino metabolic pathways involved, such as energy metabolism,
acids, lipids, and energy-related compounds. Studies oxidative stress, neurotransmission, and lipid metabolism.
have identified metabolic signatures associated with However, further validation and standardization of these
ischemic stroke and its subtypes, suggesting their metabolomic biomarkers are necessary to ensure their
potential use as diagnostic markers. 17,18 For example, clinical utility.
decreased glycerophosphocholine levels and increased In addition to diagnosis and prognosis, metabolomic
5-aminolevulinic acid levels have been suggested as markers profiling holds potential for individualized treatment
of ischemic brain injury. In addition, metabolomic strategies. By characterizing the metabolic status of
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studies have shed light on the effects of neuroprotective patients with ischemic stroke, clinicians may be able
agents and provided insights into therapeutic targets in to tailor interventions that target specific pathways or
cerebral ischemia. 20 molecules affected by cerebral ischemia. This personalized
Several metabolomic biomarkers associated with approach could potentially improve patient outcomes and
21
cerebral ischemia have been identified. Plasma samples reduce long-term disability.
from patients with ischemic stroke were analyzed by Despite the growing body of evidence supporting the
liquid chromatography-mass spectrometry, identifying role of metabolomic biomarkers in cerebral ischemia,
10 potential metabolic biomarkers. The results showed several challenges need to be addressed. Standardization
that decreased levels of α-ketoglutarate, glutamate, and of protocols for sample collection, storage, and analysis
phosphocholine and increased levels of phenylalanine, is crucial to ensure reproducibility and comparability
tyrosine, and diacetylspermine were significantly between different studies. Furthermore, large-scale
associated with cerebral ischemia. It has been confirmed multicenter studies involving diverse populations are
that there are changes in metabolites related to energy required to establish robust reference ranges and diagnostic
metabolism (e.g., lactate and alanine), neurotransmission thresholds.
(e.g., glutamate and γ-aminobutyric acid), and lipid
metabolism (e.g., glycerolipids and choline metabolites) in 3.4. Epigenomics biomarkers in cerebral ischemia
patients with cerebral ischemia. 21 Epigenomics investigates changes in gene expression
Oxidative stress plays a crucial role in the caused by modifications to DNA and histones. Epigenetic
pathophysiology of cerebral ischemia. The metabolic changes in cerebral ischemia have been associated with
profile of urine from patients with ischemic stroke has been both acute and chronic outcomes. DNA methylation
studied, revealing alterations in antioxidant metabolites, patterns have been identified as potential biomarkers
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including glutathione and related metabolites. These for predicting stroke risk, recurrence, and prognosis.
22
changes were attributed to a disturbance in the regulation of In addition, histone modifications, such as acetylation
oxidative stress in the ischemic brain. Furthermore, plasma and methylation, have been linked to neuroplasticity and
26
levels of sphingomyelins and phosphatidylcholines were recovery after stroke. It is noteworthy that advances in
found to be significantly reduced in patients with ischemic epigenomics, such as next-generation sequencing and
stroke, suggesting disturbances in lipid metabolism. 23 chromatin immunoprecipitation, have paved the way
for the identification of novel epigenetic biomarkers in
Metabolomic studies have also demonstrated the 27
potential of cerebrospinal fluid (CSF) as a valuable source cerebral ischemia.
for identifying biomarkers of ischemic stroke. In one The integration of omic data as biomarkers in cerebral
study, CSF metabolites were analyzed using nuclear MRS, ischemia has the potential to revolutionize not only
and several metabolites, including lactate, succinate, early diagnosis and prognosis but also the development
acetate, and glutamine, were identified to be significantly of personalized therapeutic approaches. Genomics,
altered in patients with ischemic stroke compared to transcriptomics, proteomics, metabolomics, and
control subjects. These metabolites are involved in epigenomics together provide comprehensive insights
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energy metabolism, mitochondrial dysfunction, and into the complex molecular pathways underlying cerebral
neuroinflammation, highlighting their potential as ischemia. Future research should focus on the validation
biomarkers for ischemic stroke. and translation of omic biomarkers into clinical practice
Volume 2 Issue 3 (2024) 5 doi: 10.36922/bh.2750

