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. 2019 Nov 7;11(4):553–579. doi: 10.1007/s12975-019-00744-5

Fig. 2.

Fig. 2

The neurovascular unit (NVU) as a source of ischemic stroke biomarkers. The NVU concept has been proved useful for analysis of spatial and functional relationships among constituents of brain tissue. An important role of NVU is attributed to its characteristic morphological structures, such as tripartite synapses, astrocytic perivascular end-feet and vascular tight junctions. In accordance with the NVU concept, ischemic stroke biomarkers can be categorized as the representatives of either individual cell type or its several components. In addition, this concept enables division of ischemic stroke biomarkers into groups characterized by similar structure and functions representing the following categories: (1) neuroglial and neuronal structural proteins, (2) amino acid neurotransmitters and enzymes, (3) inflammatory mediators, and (4) neurotrophic and growth factors. While planning the research on the new ischemic stroke biomarkers, it is important to take into account that various components of NVU play different roles in the ischemic metabolic processes (e.g., oxidative and anaerobic glycolysis); signaling pathways (e.g., glutamate-glutamine shuttle, Ca2+ ion- and purines-based signaling) reveal different sensitivity to decreased cerebral blood perfusion, as well as, reveal different proliferation potential. Consequently, the NVU concept is useful for assessment of brain tissue damage, which is reflected in concentration changes of various NVU-derived biomarkers that translocate from the brain to blood and CSF. AQP4, aquaporin-4; BDNF, brain-derived neurotrophic factor; FABPs, fatty acid–binding proteins; GABA, γ-aminobutyric acid; GDNF, glial cell line–derived neurotrophic factor; GFAP, glial fibrillary acidic protein; Glu, glutamate; Gly, glycine; GS, glutamine synthetase; Il-4, interleukin-4; Il-6, interleukin-6; Il-10, interleukin-10; MMP-9, matrix metalloproteinase-9; NGF, nerve growth factor; NSE, neuron-specific enolase; S100β, S100beta protein; Ser, serine; SR, serine racemase; TNFα, tumor necrosis factor α; vWF, von Willebrand factor