Production

Choroid Plexus

Cerebrospinal fluid is generated in high capacity by an area of the ventricular system (see Circulation) known as the choroid plexus. The choroid plexus is a specialized epithelium containing a complex network of capillaries. A choroid plexus can be found in the superior part of the inferior horn of the lateral ventricles, the superior part of the third ventricle and in the fourth ventricle near the bottom of the cerebellum. The capillary beds which supply these areas provide the epithelium with ions, plasma, oxygen etc. The epithelial cells and capillary wall form an extremely thin but selective barrier between the blood and cerebrospinal fluid. Despite their close anatomical proximity blood and CSF share many physical and functional differences.

As shown in the image below the epithelium is perfectly adapted for fluid transport. The cells contain:

• Many mitochondria (M) close to both the apical and basolateral membranes supplying energy for the active transport of ions and small molecules.
• Presence of microvilli on the apical surface increasing surface area of the membrane for maximal release and re-absorption of fluid.
• Cilia on the apical surface which oscillate to produce a net flow of CSF (not shown in the image).
• A prominent nucleus with visible nucleolus, which is essential in such an active cell.

 Ultrastructure of Choroid Plexus image courtesy of Wikimedia Commons under the creative commons license.

 Ependymal Cells

The specialized epithelial cells are known as ependymal cells. These cells are a type of neuroglia (Non-neuronal support cells of the CNS). As discussed above they are highly specialized for the transport of fluids, and because of their functional similarity share many of the same features as proximal tubule cells. CSF production occurs in two stages:

• Passive filtration of fluid across the endothelial cells of the capillary, into the interstitial fluid which bathes the ependymal cells. This is achieved by a hydrostatic pressure gradient (pressure is higher in the capillary so fluid is forced from the blood into the tissue fluid).
• A regulated active secretion across a single layered epithelium (ependymal cells).

 Fluid Secretion

Fluid secretion is a highly selective process regulated by the expression of many ion channels and transporters on the basolateral and apical membranes of the ependymal cells. The basolateral channels move ions, small molecules and water out of the interstitial fluid into the epithelial cytosol, whereas the apical channels transport from the epithelial cytosol to the cerebrospinal fluid. However both are very important in the regulation of CSF pressure and concentration.

Some ions are able to travel down electrochemical gradients causing an overall net movement of Na+, K+, Cl-, HCO3- and water from the blood plasma to the cerebrospinal fluid. Na+ crosses the basolateral membrane via secondary active transport (through the Na+/H+ exchanger). The image to the right shows a detailed account of the channels and transporters expressed in ependymal cells. Aquaporins are also expressed which allow for the movement of large quantities of water across the epithelium. Tight regulation of CSF is maintained by the presence of apical channels which remove ions and small molecules from the CSF into the epithelium because the pressure and concentration of the fluid is so important in the maintenance of the central nervous system. For example increased pressure can cause a decrease in the cranial blood supply, leading eventually to neuronal death.

Ion channel expression in ependymal cells image courtesy of Wikimedia Commons under the creative commons license.