Page 16 - BH-2-3

Brain & Heart Cerebral ischemia biomarkers

in animal models of cerebral ischemia and patients with Understanding glial TNF signaling and its role as a
ischemic stroke. Cytokines contribute to BBB disruption, potential therapeutic target may open new avenues for the
66
neuronal death, and immune cell recruitment by activating treatment of cerebral ischemia.
downstream inflammatory signaling pathways.
8. Blood-based biomarkers in cerebral
7.2. Chemokines as biomarkers in cerebral ischemia ischemia

Chemokines are small chemotactic proteins that regulate Blood-based biomarkers refer to specific molecules or
the transport and activation of leukocytes in the brain. substances in the blood that can indicate the presence of a
In cerebral ischemia, chemokines such as monocyte disease or physiological condition, such as ischemic stroke.
chemoattractant protein-1 and macrophage inflammatory These biomarkers can provide valuable information about
protein-1 alpha play a crucial role in mediating the an individual’s health status, help in the early detection
infiltration of immune cells into the ischemic region. of stroke, and monitor progression and assess response
Elevated levels of these chemokines have been detected in to treatment. Blood-based biomarkers can be divided
experimental models and stroke patients, suggesting that into several categories, including the proteomic and
they may serve as biomarkers of cerebral ischemia severity metabolomic biomarkers already mentioned, as well as
and prognosis. 66 exosomes and microvesicles, soluble adhesion molecules

7.3. ROS as biomarkers in cerebral ischemia (sCAMs), and cfDNA.
ROS production increases during cerebral ischemia, 8.1. Exosomes and microvesicles as biomarkers in
leading to oxidative stress and neuronal damage. Several cerebral ischemia
studies have found increased levels of ROS and lipid Exosomes and microvesicles, which are small membrane-
peroxidation markers, such as malondialdehyde, in animal bound extracellular vesicles, have attracted considerable
models and stroke patients. 58,67,68 These markers reflect the attention due to their involvement in intercellular
extent of oxidative damage caused by neuroinflammation communication and signaling in various pathological
and could be used as biomarkers to assess the severity of conditions. These vesicles play an important role in
cerebral ischemia and monitor therapeutic interventions. intercellular communication, carrying specific cargoes such
7.4. Microglial activation markers as biomarkers in as proteins, lipids, RNAs, and miRNAs that can regulate
cerebral ischemia target cell behavior and influence disease progression. The
analysis of exosomes and microvesicles in blood samples
Microglia, the resident immune cells of the central has shown promise for the identification of disease-specific
nervous system, plays a crucial role in neuroinflammation biomarkers. 73
during cerebral ischemia. Activation of microglia is
69
associated with the release of pro-inflammatory cytokines Exosomes and microvesicles are enriched with specific
and chemokines and the phagocytosis of damaged molecules, including miRNAs and proteins, which can
neurons. Several microglia activation markers, including be isolated and analyzed for biomarker discovery. These
ionized calcium-binding adapter molecule 1, cluster of vesicles can provide information about the tissue of origin
differentiation 11b, and triggering receptor expressed and the specific pathophysiological processes occurring in
on myeloid cells 2, have been investigated as potential a particular disease. Analyzing exosomes and microvesicles
biomarkers of cerebral ischemia. 70,71 These markers provide in blood samples can provide valuable insights into disease
73
information on the degree of microglial activation and help mechanisms and potential therapeutic targets. Exosomes
assess the progression of neuroinflammation in ischemic and microvesicles, released by various cells into biofluids
brain tissue. such as blood, CSF, and urine, have the potential to serve as
minimally invasive biomarkers and are important players
7.5. Glial TNF signaling as a biomarker in cerebral in the pathophysiology of cerebral ischemia.
ischemia During cerebral ischemia, exosomes and microvesicles
New evidence suggests that the glial TNF signaling play a crucial role in cellular communication. They act
pathway is involved in the pathophysiology of cerebral as carriers of signaling molecules and transfer bioactive
ischemia. Adenosine monophosphate-activated protein molecules to recipient cells, influencing their gene
kinase (AMPK) regulates TNF-α production in glial cells expression and cellular functions. For instance, exosomes
after cerebral ischemia, leading to tissue damage. Targeting released by endothelial cells can modulate the permeability
AMPK signaling pathways has shown neuroprotective of the BBB and alter the microenvironment of the ischemic
effects in attenuating ischemia injury in animal models. brain. 73
72

Volume 2 Issue 3 (2024) 10 doi: 10.36922/bh.2750