Cerebrospinal fluid flow
Cerebrospinal fluid (CSF) is a clear, colorless plasma-like fluid that bathes the central nervous system (CNS). Cerebrospinal fluid circulates through a system of cavities found within the brain and spinal cord; ventricles, subarachnoid space of the brain and spinal cord and the central canal of the spinal cord. Most CSF is secreted by the specialized tissue called the choroid plexus, which is located within the lateral, third and fourth ventricles. The secretion of CSF equals its removal, so there is around 150-270 milliliters of cerebrospinal fluid within the CNS at all times.
The main functions of CSF are to cushion the brain and spinal cord when they’re struck with mechanical force, to provide basic immunological protection to the CNS, to remove metabolic waste, as well as to transport neuromodulators and neurotransmitters. CSF is also very useful for clinical diagnosis, and its samples are usually obtained from the subarachnoid space (SAS) by lumbar puncture.
This article will discuss the anatomy and functions of the cerebrospinal fluid flow.
|Secretion||Choroid plexus (lateral, third and fourth ventricles), interstitial space and dura of the nerve root sleeves|
|Circulation||Lateral ventricle → third ventricle → fourth ventricle → central canal of spinal cord → subarachnoid space|
|Absorption||Arachnoid granulations, choroid plexuses and glymphatics|
|Functions||Removal of waste, cushioning of brain and intracranial neurovascular structures, neutral buoyancy, electrolytic homeostasis|
- Spinal CSF
Cerebrospinal fluid is produced by a specialized tissue called the choroid plexus. Choroid plexuses are located in the walls of the lateral ventricles and in the roofs of the third and fourth ventricles. A choroid plexus shows numerous villi, via which it secretes the cerebrospinal fluid. Structurally, each villus consists of three components;
- A layer of modified ependymal cells (choroid cells), which faces the lumen of the ventricles and secretes the CSF. The cells show many apical villous projections and are tightly bound to each other via tight junctions.
- A layer of pia mater (tela choroidea)
- A fenestrated capillary directly beneath the pia mater.
Choroid cells take up various chemicals from the underlying blood vessel which they use to actively secrete the CSF. Thus, the CSF fluid is not simply an ultrafiltrate of blood but differs from it in terms of its electrolyte, glucose and protein content. The vascular source for the choroid plexuses differs between the lateral, third ventricle and the fourth ventricle.
- The anterior portions of the choroid plexuses in the lateral and third ventricles are supplied by the anterior choroidal artery (a branch of the internal carotid artery). While their posterior parts are vascularized by the posterior lateral and medial choroidal arteries (branches of the posterior cerebral artery)
- The choroid plexus in the fourth ventricle is supplied by the inferior cerebellar arteries.
Blood-brain barrier (BBB)
Besides being involved in CSF production, the layers of choroid plexus form a selectively permeable barrier called the blood-brain barrier (BBB).
To recap, from superficial to deep, the blood-brain barrier consists of:
- Choroid ependymal cells and their tight junctions
- Pia mater
- Endothelial cells of capillaries
- Basal membrane of endothelial capillary cells
The function of the blood-brain barrier is to control the movement of water and solutes into the CSF, as well as from the CSF into the neural tissue.
Need some help learning about the circulation of cerebrospinal fluid? Discover why active recall is so essential to effective anatomy learning.
Blood-CSF barrier (BCSFB)
The blood-CSF barrier is often confused for the blood-brain barrier, while in fact it is only a part of it. The blood-CSF barrier actually refers to the tight junctions between the choroid ependymal cells, which control the passage of molecules between the underlying capillaries and cerebrospinal fluid.
If it weren’t for the tight junctions (i.e. blood-CSF barrier), the particles such as electrolytes and blood cells that can pass through the fenestrae of the capillaries would enter the CSF and therefore disturb the electrolytic and biochemical equilibrium in the blood. This barrier is functionally important for the opposite direction as well, from the CSF to the capillaries; as it prevents large molecules (such as different kinds of drugs) from freely entering the brain blood vessels.
Cerebrospinal fluid is constantly produced at a secretion rate of 0.2-0.7 ml/min, meaning that there is 600–700 ml of newly produced CSF per day. Since the total volume of CSF averages around 150-270 mL, this means that the entire volume of CSF is replaced around 4 times per day.
The pathway of the cerebrospinal fluid is as follows:
- The CSF passes from the lateral ventricles to the third ventricle through the interventricular foramen (of Monro).
- From the third ventricle, the CSF flows through the cerebral aqueduct (of Sylvius) to the fourth ventricle.
- From the fourth ventricle, some CSF flows through a narrow passage called the obex and enters the central canal of the spinal cord. However, the majority of CSF passes through the apertures of the fourth ventricle; the median aperture (of Magendie) and two lateral apertures (of Luschka). Via these openings, the CSF enters the cisterna magma and cerebellopontine cisterns, respectively.
- From there, the CSF flows through the subarachnoid space of the brain and spinal cord.
- It is finally reabsorbed into the dural venous sinuses through arachnoid granulations.
There are three recognized routes through which CSF exits the subarachnoid space (SAS) to enter the cerebral venous system; arachnoid granulations, minute channels that pass through the cribriform plate of ethmoid bone, and the glymphatic system.
The majority of the cerebrospinal fluid (CSF) is absorbed into the venous system by the arachnoid granulations. The arachnoid granulations are the protrusions of the arachnoid mater that pierce the dura mater and protrude into the lumina of the dural venous sinuses. The core of each granulation is continuous with the subarachnoid space, thus containing the cerebrospinal fluid. The surface of each arachnoid granulation contains smaller outpouchings called arachnoid villi that increase its absorption surface.
The CSF exits the subarachnoid space by diffusing through the walls of arachnoid granulations. The arachnoid granulations provide a valvular mechanism for the flow of CSF, which allows the inflow of CSF into the bloodstream without permitting the backflow of blood into the CSF. Normally the pressure of the CSF is higher than that of the venous system, so CSF flows through the villi and granulations into the venous blood.
Learn everything about the arachnoid granulations with our articles, video tutorials, quizzes and labelled diagrams.
Minute channels in the cribriform plate
The second route consists of small channels that extend from the subarachnoid space through openings in the cribriform plate of the ethmoid bone. These channels traverse the cribriform plate together with the fila olfactoria of the olfactory nerve (CN I) and drain into the lymphatic channels of the nasal mucosa.
The third route is provided by the glymphatic system. It is a recently discovered system of channels that is formed by the astroglial cells around the pial arteries. Its function is to provide an entrance route for the CSF in exchange for the interstitial fluid of the brain and spinal cord. This means that small amounts of CSF enter the nervous tissue, whilst the same amount of interstitial fluid exits into the subarachnoid space in order to be eliminated through the dural venous sinuses.
The subarachnoid space of the spinal cord is continuous to that of the brain, so that the CSF that is produced in the brain ventricles can easily reach the spinal cord as well. Let’s recall how the CSF reaches the cavities of the spinal cord:
- It flows from the fourth ventricle into the central canal of the spinal cord through the obex
- It passes through the median aperture (of Magendie) and lateral apertures (of Luschka) to enter the interpeduncular and quadrigeminal subarachnoid cisterns. From here, it continues down through the subarachnoid space of the spinal cord.
The spinal subarachnoid space is relatively large, accommodating about half of the total volume of CSF in the CNS. It extends from the foramen magnum and ends at the level of the S2 vertebra. Below the conus medullaris, roughly at the level of L1-L2, the subarachnoid space enlarges into a dural sac called the lumbar cistern. The lumbar cistern extends from L1/L2-S2 vertebral levels and it contains the dorsal and ventral rootlets of L2-Co spinal nerves (cauda equina). It is clinically significant as it is the site of lumbar puncture (extraction of CSF for medical analyses). Given that the spinal and cranial subarachnoid spaces are continuous, the spinal CSF flows back to the cranial subarachnoid space via which it is eliminated into the dural venous sinuses.
The CSF has many protective and metabolic functions.
- The CSF acts as a shock absorber, by providing a fluid buffer and thus protecting the brain from injury.
- It provides neutral buoyancy that prevents the brain from compressing the blood vessels and cranial nerves against the internal surface of the bones of the skull.
- It removes by-products of metabolism and plays an important role in the homeostasis and metabolism of the central nervous system.
Homeostasis implies the regulation of the distribution of substances (e.g. electrolytes) between the cells of the brain and neuroendocrine factors. Slight changes in the pH or the composition of the CSF can disrupt temperature, blood pressure control and hormonal exchange in subcortical structures.
The most significant disorder of the CSF flow is hydrocephalus. Hydrocephalus is caused by excessive amounts of CSF, either caused by increased production (hypersecretory hydrocephalus), an obstruction of its flow (non-communicating or obstructive hydrocephalus), or by impaired absorption through the arachnoid villi (malabsorptive hydrocephalus). Hydrocephalus is followed by an abnormal enlargement of the head in children due to an abnormal increase in the amount of CSF. This creates increased pressure within the cranium leading to a degeneration of brain tissue.
Hydrocephalus is classified as obstructive (non-communicating) when there is an obstruction to its flow from the ventricular system to the subarachnoid space; or as communicating when such obstruction is not present. Obstructions are most likely to occur at narrow passages such as the interventricular foramen, the cerebral aqueduct, the median aperture, and lateral apertures of the fourth ventricle.
Malabsorptive hydrocephalus often arises in the aftermath of subarachnoid hemorrhage and meningitis, both of which can produce occlusive adhesions of the arachnoid granulations. It can also result from traumatic brain injury and intraventricular hemorrhage.
Hydrocephalus can also be active if the pressure inside the ventricular system is continuously elevated. Active hydrocephalus is not the same as normal pressure hydrocephalus, in which CSF pressure is only intermittently elevated.