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Brain & Heart Cerebral ischemia biomarkers

Exosomes and microvesicles are involved in the initiation Several studies have indicated the potential of sCAMs as
and propagation of neuroinflammation following cerebral diagnostic biomarkers for cerebral ischemia. For instance,
ischemia. They mediate the intercellular transfer of pro- vascular cell adhesion molecule-1 (VCAM-1) has been
inflammatory cytokines, chemokines, and immune-related shown to be elevated in ischemic stroke patients compared
miRNAs, leading to the activation of neuroinflammatory to healthy controls, with elevated levels observed within
signaling pathways. Studies have shown that the cargo of 24 h of the onset of symptoms. Intercellular adhesion
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exosomes derived from activated microglia or astrocytes molecule-1 (ICAM-1) has also been shown to be a
can influence the polarization of microglia toward pro- promising diagnostic biomarker, with significantly higher
inflammatory phenotypes or exacerbate neuroinflammation. 74 levels in ischemic stroke patients compared to controls.
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Exosomes and microvesicles derived from different cell These studies support the potential of sCAMs, such as
types, including neural stem cells, mesenchymal stem cells, VCAM-1 and ICAM-1, as complementary diagnostic
and astrocytes, have shown neuroprotective properties in biomarkers for cerebral ischemia.
experimental models of cerebral ischemia. They promote Prognostic biomarkers facilitate the prediction of the
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neurogenesis, angiogenesis, and synaptic remodeling, severity, progression, and outcome of cerebral ischemia.
thereby improving neuronal survival and functional Several studies have investigated the correlation between
recovery. These vesicles carry neurotrophic factors, sCAM levels and the clinical outcome of ischemic stroke
anti-apoptotic proteins, and miRNAs that modulate the patients. For instance, elevated levels of soluble P-selectin
neuroprotection and regeneration cascades. 15 were associated with a higher risk of recurrent stroke.
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Recent advances have highlighted the potential of using Similarly, increased levels of soluble E-selectin were found
exosomes and microvesicles as therapeutic tools in cerebral to be associated with a poorer prognosis and an increased
ischemia. These vesicles can serve as natural drug delivery risk of neurological deterioration in patients with acute
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systems due to their inherent biocompatibility and ability ischemic stroke. These results suggest that sCAMs, such
to cross the BBB. Various strategies, including genetic as soluble P-selectin and soluble E-selectin, may serve as
modification and pre-treatment of the parent cells, have prognostic biomarkers for cerebral ischemia.
been explored to enhance their therapeutic potential. Disruption of the BBB is a critical event in cerebral
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Exosomes loaded with specific cargo molecules, such as ischemia, leading to increased permeability and infiltration
growth factors or anti-inflammatory agents, have shown of inflammatory cells into the brain. Adhesion molecules
promising results in pre-clinical studies. 74,75 play an important role in regulating the integrity of the
In summary, blood-based biomarkers, such as proteomic BBB. Studies have shown that sCAMs, such as soluble
biomarkers, metabolomic biomarkers, exosomes, and ICAM-1, soluble VCAM-1, and soluble E-selectin, are
microvesicles, have revolutionized disease diagnosis, associated with BBB disruption in cerebral ischemia. For
prognosis, and treatment monitoring. These biomarkers instance, a significant increase in the concentrations of
provide non-invasive and easily accessible tools for disease soluble ICAM-1 and soluble VCAM-1 was demonstrated
detection and monitoring, enabling early intervention in patients with ischemic stroke and impaired BBB
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and better patient outcomes. However, further research compared to patients without BBB. These results suggest
and validation are needed to fully realize the potential of that sCAMs may serve as biomarkers for BBB disruption
blood-based biomarkers in clinical practice. in cerebral ischemia.

8.2. sCAMs as biomarkers in cerebral ischemia The use of sCAMs as biomarkers of cerebral ischemia
holds great promise for early diagnosis, prognostic
Recently, sCAMs have emerged as potential biomarkers assessment, and monitoring of therapeutic interventions.
of cerebral ischemia due to their involvement in the Further research is needed to validate and optimize the
inflammatory response and disruption of the BBB. utility of sCAMs as biomarkers, taking into account factors
Adhesion molecules play a crucial role in the such as the timing of sample collection, sample storage
recruitment of leukocytes, the interaction between conditions, and the influence of comorbidities.
leukocytes and endothelial cells, and the subsequent 8.3. cfDNA as a biomarker in cerebral ischemia
inflammatory cascade. Soluble forms of these adhesion
molecules can be released from the cell surface by In recent years, interest in the potential use of cfDNA
proteolytic cleavage or induced release. Elevated levels of as a biomarker in cerebral ischemia has increased, as
sCAMs have been observed in various inflammatory and it offers several advantages over traditional diagnostic
ischemic conditions, making them promising biomarkers methods. CfDNA refers to circulating DNA fragments
for cerebral ischemia. 76 released into the bloodstream following cell death or

Volume 2 Issue 3 (2024) 11 doi: 10.36922/bh.2750