The CSF has many important physiological functions due to its special location and close interaction in the brain parenchyma. The accurate interpretation of CSF parameters is invaluable as a diagnostic tool in the evaluation of many CNS diseases. In the present study, we analyzed gas tension and electrolyte parameters of CSF in adult humans to establish updated reference values and have shown a difference of electrolyte levels between CSF and blood in adult humans.
Of its important functions, the CSF regulates the distribution of substances or nutrients in different areas of the brain. It may also act as a drainage pathway for the removal of metabolic waste products from brain cells or synapses [3]. The CSF is mainly produced by the choroid plexus, which is a branched structure made up of microvilli, each of which is composed of an epithelial monolayer surrounding a core of connective tissue and blood capillaries. Maintenance the pH in the CNS within a narrow range near 7.4 is an important mechanism. Neuronal function in CNS is highly susceptible to small acid-base changes. The blood brain barrier (BBB) provides a stable environment for neural function in CNS. The changes of CSF pH are associated with the function of BBB. It is relatively easily permeable to CO2, but impermeable to hydrogen and HCO3-ions. Noticeably, the central chemoreceptors in the medulla rapidly control respiration in response to the changes in CSF pH. In our study, the pH of blood and CSF were both near neutral, and the pH of CSF was slightly alkaline than that of blood. No significant differences in the pCO2 level were observed between the 2 groups. The lower pH of blood is attributed to a decreased bicarbonate buffering capacity compared with CSF.
The concentrations of various ions in the CSF are carefully regulated. Although the composition of main ions between CSF and blood determined in different animals are similar, they are certainly not the same [8]. A similar profile of main ion concentrations are also found in the human CSF presented in our study. Specifically, the concentrations of Na+ is quite close between the blood and CSF, and the concentrations of K+ and Ca2+ are lower in the CSF, whereas the Cl− concentration is greater in the CSF. The apical membrane of the choroid plexus facing the ventricle is the actual site of CSF production. The BBB keeps the ionic composition optimal for normal synaptic signalling function by a combination of specific transporters and ion channels. The driving force for secretion of CSF into the choroid plexus is unidirectional influx by ion transporters and channels that are distributed on the blood (basolateral) and CSF (apical) sides of the epithelial layer of choroid plexus [9]. Important molecular components of monovalent ions cross the CSF side of the choroid plexus include Na+/K+ ATPase, Na+/K+/2Cl− co-transporter, and channels for the secretion of K+ and HCO3−. The Na+/K+ ATPase has important functions as pumping Na+ into CSF and the process of CSF production. It drives 3 Na+ in exchange for 2 K+ ions via energy produced by ATP hydrolysis that creates a gradient to carry Na+ ions out of the choroid plexus cells and excess K+ ions from the CSF. A Na+/K+/2Cl− co-transporter removes all the relevant ions out of the choroid plexus cells. The net effect of the transport of these ions is the unidirectional influx of NaCl and NaHCO3 into the cerebral ventricle accompanied by driving water movement from the bloodstream into the cerebral ventricle to form CSF [2, 10].
The increasing studies revealed that brain Ca2+ controls the activity of ion channels and neurotransmitter release [11]. Mg2+ and Ca2+ in serum and CSF may modulate seizure activity [12]. Magnesium can inhibit N-methyl-D-aspartate (NMDA) receptors, thus increasing anti-nociceptive and anesthetic effects of analgesics or anesthetics [13]. Administration of magnesium sulfate has neuroprotective effects in acute brain injury [14], and a recent study suggested that CSF Mg2+ concentration can be used as a surrogate marker of brain bioavailability and peripherally administered magnesium sulphate did not increase CSF the Mg2+ concentration in CSF [15]. However, the mechanisms affecting CSF Mg2+ concentration are not fully understood. Some studies showed that CSF Mg2+ concentration seemed not to be influenced by increased serum Mg2+ concentration in healthy or intracranial hypertension patients [16, 17]. The balance of CSF Mg2+ ions is primarily controlled by active transport through a specific ion channel [18], and maintained at a concentration greater than that in blood as presented in our study.
Glucose is a vital metabolic energy source for the mammalian brain, and a continuous supply of glucose is essential to maintain a normal cerebral function. Glucose from blood enters the extracellular space of the brain via the GLUT family of transporters, mainly GLUT–1 and –3, distributed on the endothelial cells of the BBB and in astrocytes [19]. In human adults, the general range for CSF glucose is about half to two thirds of that for blood glucose. In our study, the CSF/blood glucose ratio is 0.52. This ratio may decrease with elevated blood glucose levels [20]. Patients with CNS infections such as bacterial or fungal usually cause low CSF/blood glucose ratio, but viral infection may have normal CSF glucose levels. Furthermore, there is not a specific pathologic process that directly results in high CSF glucose levels. Elevated blood sugar levels may lead to higher CSF glucose levels as diabetic patients because the sugar level in the blood is usually directly proportional to that in the CSF [21].
Conclusions
Although normal CSF constituents are quite similar to that of blood, there is still a small difference in normal values between them. Many CNS disorders may be reflected by altered CSF characteristics. Analysis of CSF parameters and relevant paired blood samples is highly informative, helping clinicians diagnose a variety of CNS diseases.