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Brain & Heart Cerebral ischemia biomarkers

cellular stress. These fragments originate from a variety of Future research should focus on large-scale prospective
sources, including neurons, glial cells, and blood vessels. studies to validate the diagnostic and prognostic
An ischemic insult triggers cell death pathways that lead value of cfDNA in different patient populations and to
to the release of cfDNA into the bloodstream. Numerous explore the specific cfDNA fragments associated with
studies have explored the potential of cfDNA as a the pathogenesis of cerebral ischemia. Furthermore,
biomarker for cerebral ischemia, as it is easily accessible investigating the dynamic changes in cfDNA levels
and quantifiable. during the course of cerebral ischemia could provide
valuable insights into disease progression and response
The use of cfDNA as a biomarker offers the potential
for early detection and prompt management of cerebral to treatment.
ischemia. For example, it has been shown that elevated 9. Challenges in biomarker translation
cfDNA levels in stroke patients could be detected within
the 1 h of symptom onset, allowing timely intervention Biomarkers play a vital role in the diagnosis, prognosis, and
st
and reducing the risk of long-term damage. CfDNA treatment of cerebral ischemia. They provide objective and
81
released from neutrophils into plasma during stroke is a measurable indicators of biological processes, thus enabling
key player in the post-stroke inflammatory response and early detection, monitoring, and personalized treatment
has recently been shown to trigger recurrent vascular approaches. However, the translation of biomarkers from
events through an inflammasome-dependent mechanism the laboratory to clinical practice is associated with various
leading to rupture of atherosclerotic plaques. 82,83 These challenges. This review discusses three major challenges in
examples represent initial approaches for a new, targeted biomarker translation: standardization and reproducibility,
approach to secondary stroke prevention. methodological limitations, and cost and accessibility
(Figure 2).
Ischemic stroke can occur in various subtypes,
including large artery atherosclerosis, cardioembolism, 9.1. Standardization and reproducibility
small vessel occlusion, and stroke of other etiologies. Standardization and reproducibility are major challenges
Accurate identification of stroke subtypes is crucial for in the translation of biomarkers. Biomarker discovery
the selection of appropriate treatment. Specific cfDNA and validation studies often use different platforms,
fragments have been associated with different stroke sample types, and statistical methods across different
subtypes, emphasizing the potential of cfDNA as a tool to research laboratories. This lack of standardization
differentiate stroke subtypes. 84 makes it difficult to compare and validate biomarker
Determining the severity of cerebral ischemia is crucial results between different studies. In addition, the lack of
for optimizing treatment strategies. It has been shown that reproducibility of biomarker studies has raised concerns
increased cfDNA levels are associated with larger ischemic about the reliability and validity of these biomarkers.
lesion volumes and higher stroke severity, indicating Many biomarker candidates fail to replicate their original
their potential as a biomarker for assessing the extent and results in independent validation studies, leading to
severity of cerebral ischemia. 85 false positive or false negative results. This inconsistency
A prognostic assessment is essential for estimating the
long-term outcomes of stroke patients. Several studies have
shown a correlation between cfDNA levels and functional
outcomes after cerebral ischemia. For instance, higher
cfDNA levels have been associated with poor functional
outcomes, highlighting the potential use of cfDNA as a
prognostic marker in cerebral ischemia. 86
Despite the promising potential of cfDNA as a
biomarker in cerebral ischemia, several challenges need
to be addressed before widespread clinical application.
These challenges include the standardization of cfDNA
extraction and quantification methods, the establishment
of reference ranges for cfDNA levels in healthy individuals
and stroke patients, and the assessment of the influence
of confounding factors such as age, comorbidities, and
medication use on cfDNA levels. Figure 2. Major challenges in biomarker translation

Volume 2 Issue 3 (2024) 12 doi: 10.36922/bh.2750