Cerebrospinal fluid

Cerebrospinal fluid (CSF) is a clear, colorless transcellular body fluid found within the meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricles of the brain.

CSF is mostly produced by specialized ependymal cells in the choroid plexuses of the ventricles of the brain, and absorbed in the arachnoid granulations. It is also produced by ependymal cells in the lining of the ventricles. In humans, there is about 125 mL of CSF at any one time, and about 500 mL is generated every day. CSF acts as a shock absorber, cushion or buffer, providing basic mechanical and immunological protection to the brain inside the skull. CSF also serves a vital function in the cerebral autoregulation of cerebral blood flow.

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 fills the ventricles of the brain, cisterns, and sulci, 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. The ependymal cells of the choroid plexus have multiple motile cilia on their apical surfaces that beat to move the CSF through the ventricles.

A sample of CSF can be taken from around the spinal cord via lumbar puncture. This can be used to test the intracranial pressure, as well as indicate diseases including infections of the brain or the surrounding meninges.

Although noted by Hippocrates, it was forgotten for centuries, though later was described in the 18th century by Emanuel Swedenborg.<ref>Template:Cite journal</ref> In 1914, Harvey Cushing demonstrated that CSF is secreted by the choroid plexus.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Structure

Circulation

File:NPH MRI 272 GILD.gif

MRI showing pulsation of CSF

File:Dist vent.png

Distribution of CSF

In humans, there is about 125–150 mL of CSF at any one time.<ref name="WRIGHT2012" /> This CSF circulates within the ventricular system of the brain. The ventricles are a series of cavities filled with CSF. The majority of CSF is produced from within the two lateral ventricles. From here, CSF passes through the interventricular foramina to the third ventricle, then the cerebral aqueduct to the fourth ventricle. From the fourth ventricle, the fluid passes into the subarachnoid space through four openingsTemplate:Sndthe central canal of the spinal cord, the median aperture, and the two lateral apertures.<ref name="WRIGHT2012" /> CSF is present within the subarachnoid space, which covers the brain and spinal cord, and stretches below the end of the spinal cord to the sacrum.<ref name="WRIGHT2012" /><ref name=GH2005/> There is a connection from the subarachnoid space to the bony labyrinth of the inner ear making the cerebrospinal fluid continuous with the perilymph in 93% of people.<ref name="SAKKA2011">Template:Cite journal</ref>

CSF moves in a single outward direction from the ventricles, but multidirectionally in the subarachnoid space.<ref name="Proulx2021">Template:Cite journal</ref><ref name="SAKKA2011"/> The flow of cerebrospinal fluid is pulsatile, driven by the cardiac cycle.<ref name="Mestre2018">Template:Cite journal</ref> The flow of CSF through perivascular spaces in the brain (surrounding the cerebral arteries) is obtained through the pumping movements of the walls of the arteries.<ref name="Mestre2018"/>

Contents

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. Due to the way it is produced, CSF has a lower chloride level than plasma, and a higher sodium level.<ref name=GH2005/><ref name=SALADIN2012 />

CSF contains approximately 0.59% plasma proteins, or approximately 15 to 40 mg/dL, depending on sampling site.<ref name="pmid4456012">Template:Cite journal</ref> In general, globular proteins and albumin are in lower concentration in ventricular CSF compared to lumbar or cisternal fluid.<ref>Template:Cite journal</ref> Template:Anchor This continuous flow into the venous system dilutes the concentration of larger, lipid-insoluble molecules penetrating the brain and CSF.<ref name="pmid10027064">Template:Cite journal</ref> CSF is normally free of red blood cells and at most contains fewer than 5 white blood cells per mm³ (if the white cell count is higher than this it constitutes pleocytosis and can indicate inflammation or infection).<ref>Template:Cite book</ref>

Development

At around the fifth week of its development, the embryo is a three-layered disc, covered with ectoderm, mesoderm and endoderm. A tube-like formation develops in the midline, called the notochord. The notochord releases extracellular molecules that affect the transformation of the overlying ectoderm into nervous tissue.<ref name=LARSEN2009/> The neural tube, forming from the ectoderm, contains CSF prior to the development of the choroid plexuses.<ref name="SAKKA2011"/> The open neuropores of the neural tube close after the first month of development, and CSF pressure gradually increases.<ref name="SAKKA2011"/>

By the fourth week of embryonic development the brain has begun to develop. Three swellings (primary brain vesicles), have formed within the embryo around the canal, near to where the head will develop. These swellings represent different components of the central nervous system: the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain).<ref name=LARSEN2009/> Subarachnoid spaces are first evident around the 32nd day of development near the rhombencephalon; circulation is visible from the 41st day.<ref name="SAKKA2011"/> At this time, the first choroid plexus can be seen, found in the fourth ventricle, although the time at which they first secrete CSF is not yet known.<ref name="SAKKA2011"/>

The developing forebrain surrounds the neural cord. As the forebrain develops, the neural cord within it becomes a ventricle, ultimately forming the lateral ventricles. Along the inner surface of both ventricles, the ventricular wall remains thin, and a choroid plexus develops, producing and releasing CSF.<ref name=LARSEN2009 /> CSF quickly fills the neural canal.<ref name=LARSEN2009>Template:Cite bookTemplate:Page needed</ref> Arachnoid villi are formed around the 35th week of development, with arachnoid granulations noted around the 39th, and continuing developing until 18 months of age.<ref name="SAKKA2011"/>

The subcommissural organ secretes SCO-spondin, which forms Reissner's fiber within CSF assisting movement through the cerebral aqueduct. It is present in early intrauterine life but disappears during early development.<ref name="SAKKA2011"/>

Physiology

Function

CSF serves several purposes:

1. Buoyancy: The actual mass of the human brain is about 1400–1500 grams, but its net weight suspended in CSF is equivalent to a mass of 25–50 g.<ref>Template:Cite book</ref><ref name="WRIGHT2012">Template:Cite journal</ref> 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.<ref name=SALADIN2012 />
2. 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.<ref name=WRIGHT2012 /><ref name=SALADIN2012 />
3. Prevention of brain ischemia: The prevention of brain ischemia is aided by decreasing the amount of CSF in the limited space inside the skull. This decreases total intracranial pressure and facilitates blood perfusion.<ref name="WRIGHT2012" />
4. Regulation: CSF allows for the homeostatic regulation of the distribution of substances between cells of the brain,<ref name="SAKKA2011"/> and 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 fainting.<ref name="SALADIN2012" />
5. Clearing waste: CSF allows for the removal of waste products from the brain,<ref name=WRIGHT2012 /> and is critical in the brain's lymphatic system, called the glymphatic system.<ref name=Iliff>Template:Cite journal</ref> Metabolic waste products diffuse rapidly into CSF and are removed into the bloodstream as CSF is absorbed.<ref>Template:Cite book</ref> When this goes awry, CSF can become toxic, such as in amyotrophic lateral sclerosis, the most common form of motor neuron disease.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Production

Comparison of serum and cerebrospinal fluid

Substance	CSF	Serum
Water content (% wt)	99	93
Protein (mg/dL)	35	7000
Glucose (mg/dL)	60	90
Osmolarity (mOsm/L)	295	295
Sodium (mEq/L)	138	138
Potassium (mEq/L)	2.8	4.5
Calcium (mEq/L)	2.1	4.8
Magnesium (mEq/L)	2.0–2.5<ref>Template:Cite book</ref>	1.7
Chloride (mEq/L)	119	102
pH	7.33	7.41
Template:Further-text

The brain produces roughly 500 mL of cerebrospinal fluid per day at a rate of about 20 mL an hour.<ref name="Czarniak">Template:Cite journal</ref> This transcellular fluid is constantly reabsorbed, so that only 125–150 mL is present at any one time.<ref name="WRIGHT2012" />

CSF volume is higher on a mL per kg body weight basis in children compared to adults. Infants have a CSF volume of 4 mL/kg, children have a CSF volume of 3 mL/kg, and adults have a CSF volume of 1.5–2 mL/kg. A high CSF volume is why a larger dose of local anesthetic, on a mL/kg basis, is needed in infants.<ref>Template:Cite journal</ref> Additionally, the larger CSF volume may be one reason as to why children have lower rates of postdural puncture headache.<ref name="pmid12655411">Template:Cite journal</ref>

Most (about two-thirds to 80%) of CSF is produced by the choroid plexus.<ref name="WRIGHT2012" /><ref name=GH2005/> 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, and the frontal and occipital horns of the lateral ventricles.<ref name=Young292>Template:Cite book</ref> CSF is mostly produced by the lateral ventricles.<ref name="Czarniak"/> 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.<ref name=GH2005>Template:Cite book</ref>

CSF is produced by the choroid plexus in two steps. Firstly, a filtered form of plasma moves from fenestrated capillaries in the choroid plexus into an interstitial space,<ref name="WRIGHT2012" /> with movement guided by a difference in pressure between the blood in the capillaries and the interstitial fluid.<ref name="SAKKA2011"/> This fluid then needs to pass through the epithelium cells lining the choroid plexus into the ventricles, an active process requiring the transport of sodium, potassium and chloride that draws water into CSF by creating osmotic pressure.<ref name="SAKKA2011"/> Unlike blood passing from the capillaries into the choroid plexus, the epithelial cells lining the choroid plexus contain tight junctions between cells, which act to prevent most substances flowing freely into CSF.<ref name="Hall">Template:Cite book</ref> Cilia on the apical surfaces of the ependymal cells beat to help transport the CSF.<ref name="Kishimoto">Template:Cite journal</ref>

Water and carbon dioxide from the interstitial fluid diffuse into the epithelial cells. Within these cells, carbonic anhydrase converts the substances into bicarbonate and hydrogen ions. These are exchanged for sodium and chloride on the cell surface facing the interstitium.<ref name="SAKKA2011"/> Sodium, chloride, bicarbonate and potassium are then actively secreted into the ventricular lumen.<ref name=GH2005/><ref name="SAKKA2011"/> This creates osmotic pressure and draws water into CSF,<ref name=GH2005/> facilitated by aquaporins.<ref name="SAKKA2011"/> CSF contains many fewer protein anions than blood plasma. Protein in the blood is primarily composed of anions where each anion has many negative charges on it.<ref>Template:Cite journal</ref> As a result, to maintain electroneutrality blood plasma has a much lower concentration of chloride anions than sodium cations. CSF contains a similar concentration of sodium ions to blood plasma but fewer protein cations and therefore a smaller imbalance between sodium and chloride resulting in a higher concentration of chloride ions than plasma. This creates an osmotic pressure difference with the plasma. CSF has less potassium, calcium, glucose and protein.<ref name=SALADIN2012>Template:Cite book</ref> Choroid plexuses also secrete growth factors, iodine,<ref>Template:Cite journal</ref> vitamins B₁, B₁₂, C, folate, beta-2 microglobulin, arginine vasopressin and nitric oxide into CSF.<ref name="SAKKA2011"/> A Na-K-Cl cotransporter and Na/K ATPase found on the surface of the choroid endothelium, appears to play a role in regulating CSF secretion and composition.<ref name="SAKKA2011"/><ref name="WRIGHT2012" /> It has been hypothesised 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.<ref name="pmc4118619">Template:Cite journal</ref>

There are circadian variations in CSF secretion, with the mechanisms not fully understood, but potentially relating to differences in the activation of the autonomic nervous system over the course of the day.<ref name="SAKKA2011"/>

Choroid plexus of the lateral ventricle produces CSF from the arterial blood provided by the anterior choroidal artery.<ref>Template:Cite journal</ref> In the fourth ventricle, CSF is produced from the arterial blood from the anterior inferior cerebellar artery (cerebellopontine angle and the adjacent part of the lateral recess), the posterior inferior cerebellar artery (roof and median opening), and the superior cerebellar artery.<ref>Template:Cite journal</ref>

Reabsorption

CSF returns to the vascular system by entering the dural venous sinuses via arachnoid granulations.<ref name=GH2005/> These are outpouchings of the arachnoid mater into the venous sinuses around the brain, with valves to ensure one-way drainage.<ref name=GH2005/> This occurs because of a pressure difference between the arachnoid mater and venous sinuses.<ref name="SAKKA2011"/> CSF has also been seen to drain into lymphatic vessels,<ref name="pmid15624320">Template:Cite journal</ref> particularly those surrounding the nose via drainage along the olfactory nerve through the cribriform plate. The pathway and extent are currently not known,<ref name="WRIGHT2012" /> but may involve CSF flow along some cranial nerves and be more prominent in the neonate.<ref name="SAKKA2011"/> CSF turns over at a rate of three to four times a day.<ref name=GH2005/> CSF has also been seen to be reabsorbed through the sheathes of cranial and spinal nerve sheathes, and through the ependyma.<ref name="SAKKA2011"/>

Regulation

The composition and rate of CSF generation are influenced by hormones and the content and pressure of blood and CSF.<ref name="SAKKA2011"/> For example, when CSF pressure is higher, there is less of a pressure difference between the capillary blood in choroid plexuses and CSF, decreasing the rate at which fluids move into the choroid plexus and CSF generation.<ref name="SAKKA2011"/> The autonomic nervous system influences choroid plexus CSF secretion, with activation of the sympathetic nervous system decreasing secretion and the parasympathetic nervous system increasing it.<ref name="SAKKA2011"/> Changes in the pH of the blood can affect the activity of carbonic anhydrase, and some drugs (such as furosemide, acting on the Na-K-Cl cotransporter) have the potential to impact membrane channels.<ref name="SAKKA2011"/>

Clinical significance

Pressure

Template:Further CSF pressure, as measured by lumbar puncture, is 10–18 cmH₂O (8–15 mmHg or 1.1–2 kPa) with the patient lying on the side and 20–30 cmH₂O (16–24 mmHg or 2.1–3.2 kPa) with the patient sitting up.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In newborns, CSF pressure ranges from 8 to 10 cmH₂O (4.4–7.3 mmHg or 0.78–0.98 kPa). Most variations are due to coughing or internal compression of jugular veins in the neck. When lying down, the CSF pressure as estimated by lumbar puncture is similar to the intracranial pressure.

Hydrocephalus is an abnormal accumulation of CSF in the ventricles of the brain.<ref name=DAVIDSONS2010B>Template:Cite book</ref> Hydrocephalus can occur because of obstruction of the passage of CSF, such as from an infection, injury, mass, or congenital abnormality.<ref name=DAVIDSONS2010B /><ref name=NIH2017 /> Hydrocephalus without obstruction associated with normal CSF pressure may also occur.<ref name=DAVIDSONS2010B /> Symptoms can include problems with gait and coordination, urinary incontinence, nausea and vomiting, and progressively impaired cognition.<ref name=NIH2017 /> In infants, hydrocephalus can cause an enlarged head, as the bones of the skull have not yet fused, seizures, irritability and drowsiness.<ref name=NIH2017 /> A CT scan or MRI scan may reveal enlargement of one or both lateral ventricles, or causative masses or lesions,<ref name=DAVIDSONS2010B /><ref name=NIH2017 /> and lumbar puncture may be used to demonstrate and in some circumstances relieve high intracranial pressure.<ref name=HARRISONS2015>Template:Cite book</ref> Hydrocephalus is usually treated through the insertion of a shunt, such as a ventriculo-peritoneal shunt, which diverts fluid to another part of the body.<ref name=DAVIDSONS2010B /><ref name="NIH2017">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Idiopathic intracranial hypertension is a condition of unknown cause characterized by a rise in CSF pressure. It is associated with headaches, double vision, difficulties seeing, and a swollen optic disc.<ref name=DAVIDSONS2010B /> It can occur in association with the use of vitamin A and tetracycline antibiotics, or without any identifiable cause at all, particularly in younger obese women.<ref name=DAVIDSONS2010B /> Management may include ceasing any known causes, a carbonic anhydrase inhibitor such as acetazolamide, repeated drainage via lumbar puncture, or the insertion of a shunt such as a ventriculo-peritoneal shunt.<ref name=DAVIDSONS2010B />

CSF leak

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} CSF can leak from the dura as a result of different causes such as physical trauma or a lumbar puncture, or from no known cause when it is termed a spontaneous cerebrospinal fluid leak.<ref name=DAVIDSONS2010 /> It is usually associated with intracranial hypotension: low CSF pressure.<ref name=HARRISONS2015 /> It can cause headaches, made worse by standing, moving and coughing,<ref name=HARRISONS2015 /> as the low CSF pressure causes the brain to "sag" downwards and put pressure on its lower structures.<ref name=HARRISONS2015 /> If a leak is identified, a beta-2 transferrin test of the leaking fluid, when positive, is highly specific and sensitive for the detection for CSF leakage.<ref name=DAVIDSONS2010>Template:Cite book</ref> Medical imaging such as CT scans and MRI scans can be used to investigate for a presumed CSF leak when no obvious leak is found but low CSF pressure is identified.<ref name="PALDINO2003">Template:Cite journal</ref> Caffeine, given either orally or intravenously, often offers symptomatic relief.<ref name=PALDINO2003 /> Treatment of an identified leak may include injection of a person's blood into the epidural space (an epidural blood patch), spinal surgery, or fibrin glue.<ref name=PALDINO2003 />

Lumbar puncture

File:4 vials of human cerebrospinal fluid.jpg

Vials containing human cerebrospinal fluid

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} CSF can be tested for the diagnosis of a variety of neurological diseases, usually obtained by a procedure called lumbar puncture.<ref name=AMP2003>Template:Cite journal</ref> Lumbar puncture is carried out under sterile conditions by inserting a needle into the subarachnoid space, usually between the third and fourth lumbar vertebrae. CSF is extracted through the needle, and tested.<ref name=DAVIDSONS2010 /> About one third of people experience a headache after lumbar puncture,<ref name=DAVIDSONS2010 /> and pain or discomfort at the needle entry site is common. Rarer complications may include bruising, meningitis or ongoing post lumbar-puncture leakage of CSF.<ref name=WRIGHT2012/>

Testing often includes observing the colour of the fluid, measuring CSF pressure, and counting and identifying white and red blood cells within the fluid; measuring protein and glucose levels; and culturing the fluid.<ref name=DAVIDSONS2010 /><ref name="AMP2003" /> The presence of red blood cells and xanthochromia may indicate subarachnoid hemorrhage; whereas central nervous system infections such as meningitis, may be indicated by elevated white blood cell levels.<ref name=AMP2003/> A CSF culture may yield the microorganism that has caused the infection,<ref name="DAVIDSONS2010"/> or PCR may be used to identify a viral cause.<ref name="AMP2003" /> Investigations to the total type and nature of proteins reveal point to specific diseases, including multiple sclerosis, paraneoplastic syndromes, systemic lupus erythematosus, neurosarcoidosis, cerebral angiitis;<ref name="WRIGHT2012" /> and specific antibodies such as aquaporin-4 may be tested for to assist in the diagnosis of autoimmune conditions.<ref name=WRIGHT2012/> A lumbar puncture that drains CSF may also be used as part of treatment for some conditions, including idiopathic intracranial hypertension and normal pressure hydrocephalus.<ref name=WRIGHT2012/>

Lumbar puncture can also be performed to measure the intracranial pressure, which might be increased in certain types of hydrocephalus. However, a lumbar puncture should never be performed if increased intracranial pressure is suspected due to certain situations such as a tumour, because it can lead to fatal brain herniation.<ref name=DAVIDSONS2010 />

Anesthesia and chemotherapy

Template:See also Some anesthetics and chemotherapy drugs are injected intrathecally into the subarachnoid space, where they spread around CSF, meaning substances that cannot cross the blood–brain barrier can still be active throughout the central nervous system.<ref name=HOCKING2004/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Baricity refers to the density of a substance compared to the density of human cerebrospinal fluid and is used in regional anesthesia to determine the manner in which a particular drug will spread in the intrathecal space.<ref name="HOCKING2004">Template:Cite journal</ref>

Liquorpheresis

Liquorpheresis is the process of filtering the CSF in order to clear it from endogen or exogen pathogens. It can be achieved by means of fully implantable or extracorporeal devices, though the technique remains experimental today.<ref>Template:Cite book</ref>

CSF drug delivery

CSF drug delivery refers to a number of methods designed to administer therapeutic agents directly into the CSF, bypassing the BBB to achieve higher drug concentrations in the CNS. This technique is particularly beneficial for treating neurological disorders such as brain tumors, infections, and neurodegenerative diseases. Intrathecal injection, where drugs are injected directly into the CSF via the lumbar region, and intracerebroventricular injection, targeting the brain's ventricles, are common approaches. These methods ensure that drugs can reach the CNS more effectively than systemic administration, potentially improving therapeutic outcomes and reducing systemic side effects. Advances in this field are driven by ongoing research into novel delivery systems and drug formulations, enhancing the precision and efficacy of treatments. Intrathecal pseudodelivery refers to a particular drug delivery method where the therapeutic agent is introduced into a reservoir connected to the intrathecal space, rather than being released into the CSF and distributed throughout the CNS. In this approach, the drug interacts with its target within the reservoir, allowing for changing the composition of the CSF without systemic release. This method can be advantageous for maximizing efficacy and minimizing systemic side effects. <ref>Template:Cite journal</ref>

History

Various comments by ancient physicians have been read as referring to CSF. Hippocrates discussed "water" surrounding the brain when describing congenital hydrocephalus, and Galen referred to "excremental liquid" in the ventricles of the brain, which he believed was purged into the nose. But for some 16 intervening centuries of ongoing anatomical study, CSF remained unmentioned in the literature. This is perhaps because of the prevailing autopsy technique, which involved cutting off the head, thereby removing evidence of CSF before the brain was examined.<ref name=CSFhistory />

The modern rediscovery of CSF is credited to Emanuel Swedenborg. In a manuscript written between 1741 and 1744, unpublished in his lifetime, Swedenborg referred to CSF as "spirituous lymph" secreted from the roof of the fourth ventricle down to the medulla oblongata and spinal cord. This manuscript was eventually published in translation in 1887.<ref name=CSFhistory>Template:Cite journal</ref>

Albrecht von Haller, a Swiss physician and physiologist, made note in his 1747 book on physiology that the "water" in the brain was secreted into the ventricles and absorbed in the veins, and when secreted in excess, could lead to hydrocephalus.<ref name=CSFhistory/> François Magendie studied the properties of CSF by vivisection. He discovered the foramen Magendie, the opening in the roof of the fourth ventricle, but mistakenly believed that CSF was secreted by the pia mater.<ref name=CSFhistory/>

Thomas Willis (noted as the discoverer of the circle of Willis) made note of the fact that the consistency of CSF is altered in meningitis.<ref name=CSFhistory/> In 1869 Gustav Schwalbe proposed that CSF drainage could occur via lymphatic vessels.<ref name="WRIGHT2012" />

In 1891, W. Essex Wynter began treating tubercular meningitis by removing CSF from the subarachnoid space, and Heinrich Quincke began to popularize lumbar puncture, which he advocated for both diagnostic and therapeutic purposes.<ref name=CSFhistory/> In 1912, a neurologist William Mestrezat gave the first accurate description of the chemical composition of CSF.<ref name=CSFhistory/> In 1914, Harvey W. Cushing published conclusive evidence that CSF is secreted by the choroid plexus.<ref name=CSFhistory/>

Other animals

During phylogenesis, CSF is present within the neuraxis before it circulates.<ref name="SAKKA2011"/> The CSF of teleost fish, which do not have a subarachnoid space, is contained within the ventricles of their brains.<ref name="SAKKA2011"/> In mammals, where a subarachnoid space is present, CSF is present in it.<ref name="SAKKA2011"/> Absorption of CSF is seen in amniotes and more complex species, and as species become progressively more complex, the system of absorption becomes progressively more enhanced, and the role of spinal epidural veins in absorption plays a progressively smaller and smaller role.<ref name="SAKKA2011"/>

The amount of cerebrospinal fluid varies by size and species.<ref name="REECE2013">Template:Cite book</ref> In humans and other mammals, cerebrospinal fluid turns over at a rate of 3–5 times a day.<ref name=REECE2013 /> Problems with CSF circulation, leading to hydrocephalus, can occur in other animals as well as humans.<ref name=REECE2013 />

See also

• Neuroglobin
• Pandy's test
• Reissner's fiber
• Syrinx (medicine)

External links

• Circulation of Cerebrospinal Fluid (CSF)Template:Snd interactive tool
• Cerebrospinal fluidTemplate:Snd course material in neuropathology
• Identification of the Cerebrospinal Fluid System Dynamics