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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.
53
BBB integrity in experimental models of ischemic stroke.
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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
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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
56
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

