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Brain & Heart                                                               Cerebral ischemia biomarkers



            challenges remain to be addressed. Validation studies in   promise in pre-clinical studies, and ongoing clinical trials
            larger patient cohorts are needed to confirm the diagnostic   are investigating their potential therapeutic applications. 53
            accuracy and prognostic value of these biomarkers. In   MiRNAs have great potential as biomarkers for
            addition,  standardization  of  detection  methods  and   cerebral ischemia due to their stability, tissue specificity,
            the establishment of reference ranges are essential for   and involvement in important cellular signaling pathways.
            widespread clinical application. Future research should   Numerous  studies  have identified  specific  miRNAs that
            focus on elucidating the underlying mechanisms of FOXF2   exhibit dysregulated expression during cerebral ischemia,
            and ATP5H in cerebral ischemia to develop targeted   suggesting their  potential as  diagnostic  and prognostic
            therapeutic strategies.                            markers. In addition, miRNAs represent a new avenue
            5.3. MicroRNAs as biomarkers in cerebral ischemia  for therapeutic interventions and provide hope for
                                                               improved outcomes in patients with cerebral ischemia.
            MicroRNAs (miRNAs) are small non-coding RNAs that   Future research should focus on validating these miRNA
            regulate gene expression post-transcriptionally. Since   biomarkers in larger cohorts and exploring their potential
            miRNAs are stable in blood and readily measurable,   as therapeutic targets to accelerate clinical translation.
            they have proven to be attractive biomarkers for disease
            detection and monitoring. Dysregulation of miRNAs   5.4. Apolipoprotein E (APOE) gene as a biomarker in
            has been observed in cerebral ischemia and is thought   cerebral ischemia
            to contribute to the pathological processes in stroke. For   The  APOE gene is one of the most extensively studied
            instance, miR-124 and miR-21, known for their roles in   genes in cerebral ischemia. The APOE-ε4 allele has been
            regulating apoptosis and oxidative stress, have been shown   consistently associated with an increased risk of developing
            to modulate neuronal survival, neuroinflammation, and   cerebral ischemia, particularly in younger individuals.
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            BBB integrity in experimental models of ischemic stroke.
                                                         47
            Moreover, circulating miRNAs such as miR-126, miR-134,   In addition, the  APOE-ε4 allele has been associated
            and miR-223 have been investigated as potential diagnostic   with poorer outcomes and increased mortality in stroke
                                                               patients.  Therapies targeting the APOE signaling pathway
                                                                      54
            and prognostic biomarkers for cerebral ischemia. 48,49
                                                               are being explored as potential treatment strategies for
              Another miRNA, miR-146a, is associated with the   cerebral ischemia.
            regulation of inflammation and immune responses.
            Elevated levels of miR-146a have been observed in both   5.5. Genes in the renin-angiotensin-aldosterone
            animal models and stroke patients, suggesting its potential   system (RAAS) as biomarkers in cerebral ischemia
            as a diagnostic and prognostic marker for cerebral   Genes involved in the RAAS play a crucial role in the
            ischemia.  Other miRNAs, such as miR-9, miR-124,   regulation of blood pressure and fluid balance. Genetic
                   50
            miR-210, and miR-424, have been investigated for their   variations in the ACE and angiotensinogen (AGT) genes
            potential as biomarkers. These miRNAs have been found   have been associated with an increased risk of cerebral
            to be dysregulated in animal models or in patients with   ischemia.  These variations affect the function and
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            cerebral ischemia, providing insights into the complex   production of key molecules in the RAAS cascade, resulting
            molecular mechanisms underlying ischemic injury. 51  in altered vascular tone and increased susceptibility to
              The identification of miRNA biomarkers promises   ischemic events.
            to improve the diagnosis and management of cerebral
            ischemia. MiRNAs can be detected in various body fluids,   5.6. Summary of genetic biomarkers in cerebral
            including blood, plasma, serum, and CSF, making them   ischemia
            attractive candidates for non-invasive diagnostics. Several   In summary, genetic biomarkers provide unique
            studies have demonstrated the diagnostic and prognostic   opportunities for stroke risk stratification, personalized
            value of miRNA biomarkers in different subtypes of   treatment, and prognosis prediction. Combining genetic
            ischemic stroke. For instance, miR-150 and miR-21 have   information with traditional risk factors can improve the
            shown the potential to differentiate cardioembolic stroke   accuracy of stroke prediction models.  Genetic biomarkers
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            from other types of ischemic stroke. 52            may also help in selecting appropriate treatment strategies
              In addition, miRNAs have been explored as potential   and identifying individuals who would benefit from
            therapeutic targets for cerebral ischemia. By modulating   preventive measures such as lifestyle modifications or
            the expression of specific miRNAs, researchers aim to   pharmacological interventions.
            attenuate ischemic injury and promote repair mechanisms.   Advances in genomic research have facilitated the
            Methods such as miRNA mimics or inhibitors have shown   development of polygenic risk scores (PRS)  for cerebral


            Volume 2 Issue 3 (2024)                         8                                doi: 10.36922/bh.2750
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