Cerebrospinal fluid (CSF) is a clear, colorless body fluid found in the brain and spinal cord. It is produced in the choroid plexuses of the ventricles of the brain. It acts as a cushion or buffer for the brain, providing basic mechanical and immunological protection to the brain inside the skull. The CSF also serves a vital function in cerebral autoregulation of cerebral blood flow.
The CSF occupies the subarachnoid space (between the arachnoid mater and the pia mater) and the ventricular system around and inside the brain and spinal cord. It constitutes the content of the ventricles, cisterns, and sulci of the brain, as well as the central canal of the spinal cord.
There is also a connection from the subarachnoid space to the bony labyrinth of the inner ear via the perilymphatic duct where the perilymph is continuous with the cerebrospinal fluid.
Cerebrospinal Fluid Structure
There is about 150mL of CSF at any one time. This CSF circulates within the ventricular system of the brain. The ventricles are a series of cavities filled with CSF, inside the brain. The majority of CSF is produced from within the two lateral ventricles. From here, the CSF passes through the interventricular foramina to the third ventricle, then the cerebral aqueduct to the fourth ventricle.
The fourth ventricle is an outpouching on the posterior part of the brainstem. From the fourth ventricle, the fluid passes through three openings to enter the subarachnoid space – these are the median aperture, and the lateral apertures. The subarachnoid space covers the brain and spinal cord. There is connection from the subarachnoid space to the bony labyrinth of the inner ear making the cerebrospinal fluid continuous with the perilymph.
A new hypothesis (Klarica and Oreskovic, 2014) poses that there is no unidirectional CSF circulation, but cardiac cycle-dependent bi-directional systolic-diastolic to-and-fro cranio-spinal CSF movements.
The CSF is derived from blood plasma and is largely similar to it, except that CSF is nearly protein-free compared with plasma and has some different electrolyte levels. Owing to the way it is produced, CSF has a higher chloride level than plasma, and an equivalent sodium level.
CSF contains approximately 0.3% plasma proteins, or approximately 15 to 40 mg/dL, depending on sampling site. In general, globular proteins and albumin are in lower concentration in ventricular CSF compared to lumbar or cisternal fluid. This continuous flow into the venous system dilutes the concentration of larger, lipid-insoluble molecules penetrating the brain and CSF.
CSF is normally free of red blood cells, and at most contains only a few white blood cells. Any white blood cell count higher than this constitutes pleocytosis.
CSF serves several purposes:
- Buoyancy: The actual mass of the human brain is about 1400 – 1500 grams; however, the net weight of the brain suspended in the CSF is equivalent to a mass of 25 – 50 grams. The brain therefore exists in neutral buoyancy, which allows the brain to maintain its density without being impaired by its own weight, which would cut off blood supply and kill neurons in the lower sections without CSF.
- Protection: CSF protects the brain tissue from injury when jolted or hit, by providing a fluid buffer that acts as a shock absorber from some forms of mechanical injury.
- Prevention of brain ischemia: The prevention of brain ischemia is made by decreasing the amount of CSF in the limited space inside the skull. This decreases total intracranial pressure and facilitates blood perfusion.
- Homeostasis: CSF flows throughout the inner ventricular system in the brain and is absorbed back into the bloodstream, rinsing the metabolic waste from the central nervous system through the blood–brain barrier. This allows for homeostatic regulation of the distribution of neuroendocrine factors, to which slight changes can cause problems or damage to the nervous system. For example, high glycine concentration disrupts temperature and blood pressure control, and high CSF pH causes dizziness and syncope. The CSF has a “sink action” by which the various substances formed in the nervous tissue during its metabolic activity diffuse rapidly into the CSF and are thus removed into the bloodstream as CSF is absorbed.
- Clearing waste: CSF provides a mechanism for the removal of waste products from the brain, CSF has been shown by the research group of Maiken Nedergaard to be critical in the brain’s glymphatic system, which plays an important role in flushing metabolic toxins or waste from the brain’s tissues’ cellular interstitial fluid. CSF flushing of wastes from brain tissue is further increased during sleep, which results from the opening of extracellular channels controlled through the contraction of glial cells, which allows for the rapid influx of CSF into the brain. These findings indicate that CSF may play a large role during sleep in clearing metabolic waste, like beta amyloid, that are produced by the activity in the awake brain. Results of Klarica et al. suggest that efflux transport at the capillary endothelium is much more important for brain homeostasis than the removal of potential toxic brain metabolites by CSF “circulation”.
The brain produces roughly 500 mL of cerebrospinal fluid per day.
Most (about two-thirds) of CSF is produced by the choroid plexus. The choroid plexus is a network of blood vessels present within sections of the four ventricles of the brain. It is present throughout the ventricular system except for the cerebral aqueduct, frontal horn of the lateral ventricle, and occipital horn of the lateral ventricle.
CSF is also produced by the single layer of column-shaped ependymal cells which line the ventricles; by the lining surrounding the subarachnoid space; and a small amount directly from the tiny spaces surrounding blood vessels around the brain.
CSF that is produced by the choroid plexus in two steps. The lining of the choroid plexus are similar to ependymal cells, except for the added presence of tight junctions, which act to prevent most substances flowing freely into the CSF. The lining cells secretes sodium into the ventricles. This creates osmotic pressure and draws water into the CSF space.
Chloride, with a negative charge, moves with the positively charged sodium and an electroneutral charge is maintained. Potassium, glucose and bicarbonate are all also transported out of the cell. As a result, CSF contains a higher concentration of sodium and chloride than blood plasma, but less potassium, calcium and glucose and protein.
Orešković and Klarica hypothesise that CSF is not primarily produced by the choroid plexus, but is being permanently produced inside the entire CSF system, as a consequence of water filtration through the capillary walls into the interstitial fluid of the surrounding brain tissue, regulated by AQP-4.
CSF returns to the vascular system by entering the dural venous sinuses via arachnoid granulations. However, some have suggested that CSF flow along the cranial nerves and spinal nerve roots allow it into the lymphatic channels; this flow may play a substantial role in CSF reabsorbtion, in particular in the neonate, in which arachnoid granulations are sparsely distributed. The flow of CSF to the nasal submucosal lymphatic channels through the cribriform plate seems to be especially important.
However, the Orešković and Klarica hypothesis, suggests that the CSF does not flow unidirectionally to cortical subarachnoid spaces to be passively absorbed through arachnoid villi, but is being permanently produced and absorbed inside the entire CSF system, as a consequence of water filtration and reabsorption through the capillary walls into the interstitial fluid of the surrounding brain tissue. CSF turns over at a rate of three to four times a day.
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