A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans

Abstract

In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning.

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

“…Subsequent studies introduced the term ‘glymphatic’ system to describe this paravascular circulation, and suggested that solute transport in the CNS occurs via CSF convective flow through the brain extracellular spaces, in a para-arterial to para-venous direction, regulated by aquaporin-4 (AQP4) water channels on astrocytes 37,38 . The proposed glymphatic mechanism, however, has not been supported by the latest studies 39–42 , and the convective, pressure-driven fluid flow of CSF from para-arterial to para-venous extracellular spaces throughout the parenchyma remains unproven 43–45,39,40 . Furthermore, deletion of Aqp4 in mice and rats does not impair the transport of fluorescent solutes from the subarachnoid space into the brain, which implies that water production by astrocyte end-feet does not have a role in the regulation of solute transport within parenchymal extracellular spaces 39 .…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…Notably, vitamin C and folate diffuse into the brain through the CSF (93,94). Many other ions and proteins are transported through the choroid plexus epithelium and diffuse from the CSF into the brain, where they affect neuronal function (94). More recently, the immune compartment in the meninges was implicated in neuronal function (75).…”

“…CSF and its constituents can act directly on brain function. Notably, vitamin C and folate diffuse into the brain through the CSF (93,94). Many other ions and proteins are transported through the choroid plexus epithelium and diffuse from the CSF into the brain, where they affect neuronal function (94).…”

Cerebrospinal fluid elemental analysis by using a total sample consumption system operated at high temperature adapted to inductively coupled plasma mass spectrometry

“…However, ICP-MS elemental analysis of this human CSF samples is complex because of several reasons: i) first the concentration of the trace elements of interest is typically very low; ii) second, no CRMs are available; 8 iii) third, ICP-MS is prone to suffer from spectral as well as non-spectral interferences caused by the CSF matrix, 10,34 which may degrade accuracy. 12 Table 1 shows examples of possible spectral interferences when analysing CSF samples.…”