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Brain & Heart                                                               Cerebral ischemia biomarkers



            pathophysiology  of  cerebral  ischemia  and  identifying   A comprehensive proteomic analysis of plasma samples
            potential biomarkers for early detection and prognosis.   from  ischemic  stroke  patients  and  healthy controls
            Genomics has revolutionized our understanding of the   identified nine significantly dysregulated proteins in the
            genetic component of cerebral ischemia and has enabled   ischemic stroke group, including vasoactive intestinal
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            the  identification of several genetic variants  associated   peptide, complement C3, and haptoglobin.  These
            with an increased risk of stroke. One notable example is the   proteins are implicated in biological processes related to
            locus 9p21, which is associated with large vessel ischemic   inflammation, oxidation, and coagulation, highlighting
            stroke and other cardiovascular diseases.  In addition, the   their potential as blood-based biomarkers of cerebral
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            identification of single nucleotide polymorphisms (SNPs)   ischemia.
            in candidate genes involved in endothelial dysfunction,   Proteomics aims to identify and quantify protein
            platelet aggregation, and lipid metabolism has contributed   expression patterns, providing valuable insights into the
            to the discovery of new therapeutic targets. 9     functional consequences of changes in gene expression.

            3.1. Transcriptomics biomarkers in cerebral ischemia  Proteomic studies have identified numerous differentially
                                                               expressed proteins associated with cerebral ischemia,
            Transcriptomics enables the study of gene expression   including matrix metalloproteinases (MMPs), heat shock
            patterns in cerebral ischemia and provides insights into the   proteins, and neuroinflammatory markers.  For example,
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            molecular mechanisms involved in ischemic injury. For   elevated levels of MMP-9 are associated with blood-
            instance, microarray analyses have revealed differentially   brain barrier (BBB) dysfunction and an increased risk of
            expressed genes involved in inflammation, neuronal   hemorrhagic transformation in ischemic stroke patients.
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            apoptosis, and oxidative stress following cerebral ischemia.   Proteomic analysis has also revealed the potential of plasma
            Researchers have identified potential biomarkers such as   biomarkers such as copeptin and miR-134 as predictors of
            pituitary adenylate cyclase-activating polypeptide and   stroke severity and patient outcomes. 15
            S100 calcium-binding protein B (S100B) as early indicators
            of ischemic brain injury. 10                         Proteomic biomarkers have shown great potential
                                                               for improving the detection, diagnosis, and monitoring
              A potential biomarker for cerebral ischemia is hypoxia-  of cerebral ischemia. Several proteomic studies have
            inducible factor 1 (HIF1). HIF1 is a transcription factor   identified  dysregulated  proteins  associated  with
            that plays a crucial role in the cellular response to low   inflammation, oxidative stress, neuronal cell death, and
            oxygen levels—hypoxia. During cerebral ischemia, the   other biological processes involved in cerebral ischemia.
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            brain is exposed to hypoxia, leading to the activation of   These biomarkers provide valuable insights into the
            HIF1. Studies have shown that serum HIF-1α is closely   pathophysiology of cerebral ischemia, aid early diagnosis,
            correlated with hemorrhagic severity and poor outcomes   and may guide targeted therapeutic approaches. However,
            and  may serve as  a  potential prognostic  biomarker  for   further research is needed to validate these proteomic
            this  condition.  In  addition,  HIF1 is  involved in  the   biomarkers and translate them into routine clinical practice
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            regulation of genes related to cell survival, angiogenesis,   for treating patients with cerebral ischemia.
            and metabolism,  all of which are important processes in
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            the pathophysiology of cerebral ischemia.          3.3. Metabolomic biomarkers in cerebral ischemia
              In addition, transcriptomic profiling has facilitated the   Conventional diagnostic imaging techniques such as CT
            discovery of genes associated with post-stroke recovery,   or  MRI  provide  valuable  information  about  the  extent
            offering potential targets for neurorestorative therapies. 8  and location of ischemic lesions. However, they lack the
                                                               ability to assess the underlying metabolic changes that
            3.2. Proteomic biomarkers in cerebral ischemia     occur during the ischemic event. Metabolomic profiling
            Proteomic  biomarkers  are  molecules  measurable  in   offers a promising approach to identifying and quantifying
            various body fluids or tissues that have shown promise in   different metabolites that may serve as biomarkers for
            elucidating the biological processes involved in cerebral   ischemic stroke.
            ischemia. A  frequently used approach for discovering   Metabolomics is a comprehensive analysis of small
            proteomic biomarkers is mass spectrometry. This    molecule metabolites (e.g., amino acids, lipids, and sugars)
            technique identifies and quantifies proteins in a sample   present  in  biological  samples.  By  analyzing  changes  in
            based on their mass-to-charge ratio. By comparing protein   the  metabolome, metabolomic studies  aim  to  unravel
            profiles between healthy individuals and those with stroke,   the  complex  metabolic  pathways  altered during cerebral
            researchers can identify potential biomarkers for further   ischemia. This approach has the potential to identify
            validation and clinical use.                       new biomarkers that can aid in the early diagnosis, risk


            Volume 2 Issue 3 (2024)                         4                                doi: 10.36922/bh.2750
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