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. 2022 Feb 22;13:805657. doi: 10.3389/fimmu.2022.805657

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Copyright © 2022 Mapunda, Tibar, Regragui and Engelhardt

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The brain barriers. The schematic coronal brain section depicts the localization of the different brain barriers shown in (A–C). (A) Barriers at the surface of the human brain. The meninges are composed of three layers, the dura mater, the arachnoid barrier, and the pia mater. The dura mater is directly connected to the skull bone. In humans, the dura mater is composed of three layers, the periosteal dura, the meningeal dura and the dural border cells. The dura mater has its own network of arteries (MA), veins (MV) and dural lymphatics (DL). The arachnoid barrier is formed by arachnoid fibroblasts which are connected by tight junctions and form a bona fide blood-cerebrospinal fluid barrier (BCSFB) – the arachnoid barrier – between the dura mater and the CSF filled subarachnoid space. Arachnoid trabeculae formed by a collagen core that is ensheathed by arachnoid and pial fibroblasts cross the SAS towards the pia mater and to the leptomeningeal blood vessels. The fibroblasts of the pia mater cover the veins and arteries in the SAS and separate the SAS from the subpial space filled with collagen bundles. The pia mater reflects of the surface where arteries dive into the brain parenchyma and at the same time ensheathes the arteries entering the brain. The glia limitans forms a barrier at all surfaces of the CNS parenchyma, this is the outer surface (glia limitians superficialis) and the perivascular surfaces (glia limitans perivascularis). (B) The blood–CSF barrier of the choroid plexus (ChP). The ChPs are localized in all four ventricles of the brain. The ChP epithelial cells are connected by unique parallel running tight junction stands and establish a BCSFB. The ChP stroma harbors dendritic cells and macrophages and the blood vessels of the ChP are fenestrated. (C) The blood–brain barrier (BBB) is formed by highly specialized microvascular endothelial cells connected by complex tight junctions. The endothelial basement membrane harbors a high number of pericytes. At the level of capillaries the endothelial basement membrane and the parenchymal basement membrane of the glia limitans merge. However that the post-capillary venule level they leave a small gap where single antigen-presenting cells can be found. The microvessels are surrounded by the glia limitans, which is composed of the parenchymal basement membrane and astrocyte end-feet. The extravasation of immune cells into the CNS parenchyma occurs at the level of postcapillary venules and thus involves crossing two barriers, the endothelial BBB and after reaching the perivascular space subsequent crossing of the glia limitans. The shapes of the cell types were adapted from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Common Attribution 3.0 Generic License.