Abstract
According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.
Highlights
The anatomy of the cerebrospinal fluid (CSF) system includes the cerebral ventricles as well as the spinal and brain subarachnoid spaces, cisterns and sulci
The discovery of aquaporins and other water transporters, all highly selective just for water molecules, implies that the extent of water exchange across the barriers may be heavily underestimated by the classical flow studies [30,49]
The notion that osmolality does not impact CSF absorption [2,33] or that CSF absorption into capillaries requires a hydraulic pressure gradient, which would cause the collapse of the vessel [47], needs to be reconsidered
Summary
The anatomy of the cerebrospinal fluid (CSF) system includes the cerebral ventricles as well as the spinal and brain subarachnoid spaces, cisterns and sulci. It has been shown that pial membranes between the PVS and the SAS could prevent the exchange of larger molecules, since tracer, following intraparenchymal injection, accumulated within the PVS but was not distributed into the cisternal CSF [80] This observation is supported by clinical findings that following aneurysmal rupture in man, red blood cells are confined to the subarachnoid space, and do not enter the VRS [76]. It has been shown both experimentally and clinically that the PVS and possibly more importantly intramural pathways between the basement membranes of the wall of arterioles and arteries provide drainage for the ISF and waste molecules of the brain. Confirmatory evidence of the impact of aquaporins on ISF regulation has been independently reported by others [115]
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