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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
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            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
                          24
            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
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