Table 1 Physico-chemical properties and physiological parameters of the CSF system

CSF Formation Rate

Produced mainly by choroid plexuses, CSF is formed at 0.4 ml/min/g in several mammals. Human production rates vary from 0.3 to 0.6 ml/min depending upon measurement method. CSF formation, an active secretion by epithelial cells, involves pumps, cotransporters & antiporters, ion channels and aquaporins [1, 77]. It is under neuroendocrine & hormonal modulation [6, 246]. Daily volume of CSF produced in adult humans is 500–600 ml.

CSF Pressure

In adult humans the normal CSFP is about 100 mm H₂O. Ventricular pressure is normally about 35 mm H₂0 in rats. CSFP is typically slightly higher than venous pressure in the dural sinuses. CSFP is stable when CSF formation and reabsorption are balanced. Elevated CSFP is reduced by acetazolamide, which inhibits formation of fluid by the choroid plexus [36, 43, 44].

CSF Flow

Flow of CSF is pulsatile [185, 192]. CSF pulsations depend upon the arterial hemodynamics in the plexus. CSF flow is from the lateral to 3^rd and 4^th ventricles. CSF flows out of 4^th ventricular foramina into basal cisterns [1]. It is then convected into the spinal and cortical subarachnoid spaces.

CSF Volume

In healthy humans, the ventricular and subarachnoid CSF spaces, respectively, are about 25% and 75% of total CSF volume [1]. Total CSF space in young adults is about 160 ml, i.e., more than half that of brain interstitial fluid volume. The ratio of CSF volume to brain volume increases in aging and neurodegeneration [9, 19].

CSF Turnover Rate

CSF turnover rate is directly proportional to CSF formation rate and inversely related to CSF volume [3]. It is an index of CSF sink action on brain interstitial solutes [33]. Clearance of brain metabolites depends on a CSF renewal of 0.3–0.4% per min. Mammalian CSF is totally replaced about 4 times each day.

CSF Composition

CSF is an active secretion, not simply a plasma ultrafiltrate [1]. Carrier transport of ions and molecules, along with molecular sieving at blood-CSF barrier, generates a CSF concentration lower than plasma in protein, K [221] & urea [33]; and higher in Cl & Mg. Disease distorts CSF chemistry, enabling CSF biomarking [227]. CSF is 99% water, compared to the 92% water of plasma.

CSF Recycling

In addition to CSF macrocirculation through ventriculo-subarachnoid spaces, there is limited microcirculation of CSF recirculated by bulk flow from the cortical subarachnoid space into Virchow-Robin perivascular spaces and then out of brain via CSF drainage routes [253–255].

CSF Reabsorption

CSF is cleared from CNS by bulk flow along sleeves of the subarachnoid space surrounding cranial nerves that enter the nose and eyes [263, 264]. Substantial drainage occurs through the cribriform plate, the CSF eventually reaching the nasal submucosa and downstream cervical lymphatics [267, 268]. CSF is also cleared along spinal nerves [279]. Lymphatic drainage of CSF needs substantiation in humans. Arachnoid villi in dural venous sinuses may serve as ancillary drainage sites when CSFP is elevated.