FIGURE 8.

Barriers separate the central nervous system (CNS) from peripheral tissues, but fluid can exchange with relative ease between all the CNS compartments due to the lack of tight barriers within the CNS. Middle: the tight barriers of the adult human brain in red and porous membranes in green. CNS is separated from peripheral tissues by several tight barriers (red lines), which include the blood brain barrier (BBB), the blood-choroid barrier, and the arachnoid membrane. Each of these barriers is created by expression of tight junctions containing claudins and other junctional proteins. The brain surfaces, i.e., the pial membrane and the ependymal cells layers covering the ventricles, are permeable membranes (green lines). Both the cells covering the ventricular surface (ependymal cells) and the cortical surfaces (pial cells) are connected by gap junctions, but gaps allow exchange of cerebral spinal fluid (CSF) with the extracellular fluid (green lines). Of note, astrocytes rather than endothelial cells form a vascular barrier in the external and intermediate zones of the median eminence and the adjacent ventral part of the arcuate nucleus, but not in other regions of the hypothalamus (187, 188). Also shown is the localization of the choroid plexus in the lateral, 3rd, and 4th ventricles, the meningeal layer, and the subarachnoid space. Top left inset: the BBB is a tight barrier that restricts fluid and solute exchange with the vascular compartment while the perivascular endfeet of astrocytes are loosely connected by gap junctions. Bottom left inset: The meningeal membranes consist of dura mater, arachnoid mater, and pia mater. The arachnoid membrane is a tight barrier expressing claudin-11 that separates the peripheral tissue and dura mater from the subarachnoid space. Pia mater covers all surfaces of the brain and spinal cord, but does not represent a barrier for fluid exchange. Together, these 2 membranes are known as the leptomeninges. Top right inset: choroid plexus is a simple structure consisting of a single layer of tight junction-coupled choroidal epithelial cells resting on a basement membrane containing a complex network of fenestrated capillaries. Bottom right inset: The brain surface is covered by loosely connected pial cells, whereas the ependymal lining of the ventricular surfaces also lacks tight junctions. Astrocytic processes contact both the pial and the ependymal layers, thereby creating a second semipermeable layer that possibly acts as a filter. Thus CSF can exchange with brain extracellular fluid at all of the brain surface.