Astrocyte–Endotheliocyte Axis in the Regulation of the Blood–Brain Barrier

The evolution of blood–brain barrier paralleled centralisation of the nervous system: emergence of neuronal masses required control over composition of the interstitial fluids. The barriers were initially created by glial cells, which employed septate junctions to restrict paracellular diffusion in the invertebrates and tight junctions in some early vertebrates. The endothelial barrier, secured by tight and adherent junctions emerged in vertebrates and is common in mammals. Astrocytes form the parenchymal part of the blood–brain barrier and commutate with endothelial cells through secretion of growth factors, morphogens and extracellular vesicles. These secreted factors control the integrity of the blood–brain barrier through regulation of expression of tight junction proteins. The astrocyte–endotheliocyte communications are particularly important in various neurological diseases associated with impairments to the blood–brain barrier. Molecular mechanisms supporting astrocyte–endotheliocyte axis in health and disease are in need of detailed characterisation.