Table 3.
Biomarkers derived from the biomarker panel proposal and their possible role identified in stroke.
| Proteins | Gene name | Protein name | Description | Functions | References |
|---|---|---|---|---|---|
| NR2 peptide | GRIN1 GRIN2A GRIN2B GRIN2C |
Glutamate receptor ionotropic, NMDA 2A, and NMDA 2B | It is a ligand-gated ion channel with high calcium permeability and voltage-dependent sensitivity to magnesium. It is essential in the process of neuronal synapses. | As a response to the brain's ischemic conditions, serine proteases are activated, which causes the cleavage of the NR2 subunit of NMDA receptors (NMDARs). Then its subunit is released to the blood, being a marker of neuronal damage. | (47) |
| GFAP | GFAP | Glial fibrillary acidic protein | It is an intermediate filament class-III. It is classified as a glial marker. | After an injury, trauma, disease, genetic disorders, or chemical insult GFAP is released from reactive astrocytes. The process is named astrogliosis and reflects structural and functional damage in the CNS. | (51, 53) |
| S100β | S100β | Protein S100-β | It is a protein-related to calcium metabolism. Also, it participates in the transmission of intracellular signals through second messengers. It is involved in the development and maintenance of the CNS. It is classified as a glial marker. | It is released from astrocytes and microglia after an injury or trauma, reflecting the CNS's structural and functional damage. It is directly related to the volume of lesions, clinical status, and functional outcome. | (29, 50) |
| vWF | VWF | von Willebrand factor | It plays an essential role in the maintenance of hemostasis, blood coagulation, and cell adhesion. | It is secreted by the endothelial cell activated in response to injury and can adhere to circulating platelets and contributing to thrombus formation. | (54) |
| MMP-9 | MMP9 | Matrix metallopeptidase 9 | It is a proteolytic enzyme belonging to the group of gelatinases. It has an essential role in local proteolysis of the extracellular matrix and leukocyte migration. | It is activated by high concentrations of oxide nitric and degrades the type IV collagen present in the endothelial blood–brain barrier, increasing its parenchymal destruction. It is related to the inflammatory response after stroke. | (52, 55) |
| IMA index (albumin) | ALB | Albumin | It is the major transporter of Zn, Ca2+, Mg in plasma and binds water Na+, K+, fatty acids, hormones, etc. It regulates the colloidal osmotic pressure of blood. | Under ischemic conditions, it is a measure of oxidative stress, where the NH2 terminus of human albumin may be modified for the free radicals, but the precise mechanism is yet unknown. | (30, 44, 56) |
| AT-III | SERPINC1 | Antithrombin III | It is a plasma serine protease inhibitor that regulates the blood coagulation cascade and inhibits the thrombin. | Inactive AT-III–thrombin complexes are formed during the acute phase of stroke. | (57, 58) |
| Fibrinogen | FGA, FGB, FGG | Fibrinogen | It is a blood glycoprotein essential in coagulation and determines the plasma viscosity. | It is related to the thrombosis process favoring the platelet aggregation after injury, being one of the primary components of blood clots. | (40, 59) |