TABLE 1.
The functions and regulators of NVU.
| NVU components | Functions | Regulators | References |
|---|---|---|---|
| Neurons | Critical in the regulation of BBB function, innervate endothelial cells and their associated astrocytes. Maintain the homeostasis of the brain microenvironment, provide nutritional support for the brainetc. | Mcl-1/Bcl-2, OXR1, P53/Caspase-3, TRAF3, ADIPOR2etc. | Awooda et al. (Awooda et al., 2015) |
| Anilkumar et al. (Anilkumar et al., 2020) | |||
| Cregan et al. (Cregan et al., 1999) | |||
| Astrocytes | As a part of the blood-brain barrier, can connect capillaries and neurons, participate in the nutritional support of neurons and the regulation of electrophysiological activities, and can secrete a large number of neurotrophic factors and growth factors to maintain the stability of the microenvironment and repair after injury | AQP-4, TLR4, TGF-β, ADIPOR2, Nrf2, ApoE, MCSF, IL-6, MCP-1, MMP-9, GFAP, GLT-1, GLAST, PARsetc. | Becerra-Calixto et al. (Becerra-Calixto and Cardona-Gomez, 2017) |
| Hiroko (Ikeshima-Kataoka, 2016) | |||
| Cekanaviciute et al. (Cekanaviciute and Buckwalter, 2016) | |||
| Microglia | As an innate immune effector cell, microglia is necessary for the normal development of the nervous system | TLR, MHC-II, CD16/32, BDNF, GDNF, VEGF, BMP-7, TGF-β, CSF-1, TNF-α, TNF-β, IGF-1, NADPH oxidase, IL-1, IL-4, IL-5, IL-6, IL-8, IL-10, pro-MMP-9, NO, ROSetc. | Kim et al. (Kim and De Vellis, 2005) |
| Hamel (Hamel, 2006) | |||
| Colonna et al. (Colonna and Butovsky, 2017) | |||
| Kang et al. (Kang et al., 2020) | |||
| Oligodendrocytes | Their main function is to wrap axons in the central nervous system, form an insulating myelin structure, assist in the efficient transmission of bioelectrical signals, maintain and protect the normal function of neurons | Nogo-A, CNTF, IGF-1, NT-3, PDGFetc. | Nave et al. (Nave and Werner, 2014) |
| Plemel et al. (Plemel et al., 2014) | |||
| Vascular endothelia cells (VECs) | As the physical barrier of the BBB, VECs are formed by preventing cells and molecules from passively entering the brain through tight junctions between cells | NF-κB, NO, Prostacyclin, EDHF, Eicosanoids, TIMP-2, VCAM-1, ICAM-1, P-selectin, MMPsetc. | Onat et al. (Onat et al., 2011) |
| Henke et al. (Henke et al., 2007) | |||
| Kathrina et al. (Marcelo et al., 2013) | |||
| Pericytes | Vital in the formation and maintenance of BBB integrity, angiogenesis, and removal of toxic substances | Angiopoientin-1, MIF, Occludin, SIPT1, MRPetc. | Rustenhoven et al. (Rustenhoven et al., 2017) |
| Hori et al. (Hori et al., 2004) | |||
| Extracellular matrix (ECM) | Mediating cell differentiation, proliferation, adhesion, morphogenesis and phenotype | Collagen, Undulin, Tenascin, Fibronectin, Dermatan sulfate, Decorinetc. | Bonnans et al. (Bonnans et al., 2014) |
| Zhang et al. (Zhang et al., 2021a) | |||
| Basal lamina | Located on the outside of the lumen of the cerebral microvascular endothelium, it is composed of extracellular matrix proteins secreted by VECs, pericytes, and astrocytes, and is involved in the regulation of vascular integrity | Collagen, Laminin, Fibronectin, Elastin, Proteoglycans, Merosin, Dystroglycan, Nidogen, Growth factors, MMPsetc. | Hoshi et al. (Hoshi and Ushiki, 2004) |
| Nguyen et al. (Nguyen et al., 2021) |