The arachnoid granulations are special one-way cerebrospinal fluid (CSF) valves. In order to exit the skull via the large dural sinuses (veins) CSF must first pass through these valves. In this regard, the arachnoid granulations serve to both limit the flow of CSF fluid into the dural sinuses, as well as to prevent the backflow of venous blood into the subarachnoid spaces.
CSF is a filtrate of blood that comes from dense beds of capillaries (arteries) called the choroid plexus. It flows out of the choroid plexus and across the blood-brain barrier to enter into the chambers in the middle of the brain called ventricles. The blood-brain barrier is a very fine sieve that filters out most of the components of blood. Essentially, what remains is water with some sugar and other elements mixed in.
The Arachnoid Villi Valves
The arachnoid granulations (CSF valves) are also known as the arachnoid villi. The arachnoid villi work somewhat similarly to tight junction connections between cells (intercellular) to limit flow across a membrane. For example, as mentioned above, the blood-brain barrier uses tight cell junctions to filter fluids before entering into the brain. Tight junctions work similar to a sifter used for fine flour. But as we learn more about their microscopic function, it appears the arachnoid granulations are more complicated than simple diffusion (passage) through tight passive filter type membranes. They also work by a process called vacuolization.
In the vacuolization process CSF gets pumped into a slit-like opening on the inside surface of the arachnoid granulations. The continued pumping and pressure of CSF causes the opening to balloon into a microscopic bubble called a vacuole. At a certain point the vacuole reaches maximum capacity which prevents further filling. The vacuole then seals itself off on the inside of the arachnoid granulation. Eventually it bursts through the outside wall of the villi and empties into the dural sinuses.
I suspect that the eruption and expulsion of CSF from the vacuole within the arachnoid villi is driven by CSF pulsations in the subarachnoid spaces. In brief, the continuous pounding on the arachnoid villi caused by CSF pulsations increases the pressure acting on the vacuole trapped inside the walls of the villi. Eventually the pressure inside the vacuole rises to a point where it overcomes the strength of the outside membrane of the villi and bursts open causing CSF to flow into the dural sinuses. As the CSF is squeezed out, the vacuole shrinks in size and disappears. This causes the tight cell junctions to snap shut and prevent backflows of venous blood into the villi. The delay between the formation and release of CSF in the vacuole would explain why CSF pulsations appear to have a different cycle than circulation and respiration. The rhythm of CSF pulsations is another topic I will cover separately as this site develops.
The role of the arachnoid granulations in hydrocephalus is unclear. When they start to function in a baby is also unclear. They don’t appear to function as much when the baby is in utero (before delivery). They seem to develop and become much more active some time after birth. It has long been suspected that they may malfunction in certain cases and cause hydrocephalus. Sometimes the arachnoid granulations become calcified, especially with aging.
After leaving the ventricles CSF flows through the subarachnoid spaces of the brain and cord before emptying into the dural sinuses. The subarachnoid space (cavity) is depicted in the darker green in the picture above. The dural sinuses are the large venous tunnels that drain the brain. The superior sagittal sinus (dural sinus), veins and venous lacunae (lakes) are all depicted in dark blue in the picture. The superior sagittal sinus, as well as the other dural sinuses are tunnels constructed from the tough outer protective coat of the brain called the dura mater, which is depicted in yellow. As mentioned above, in addition to limiting the flow of CSF into the dural sinuses, the arachnoid granulations also serve as one-way valves that prevent the back flow (inversion flow) of venous blood back into the subarachnoid spaces.
After decades of research and much closer inspection we are just beginning to understand where and how the arachnoid granulations actually work. Suffice it to say, it is far too lengthy and complex a subject to go into in detail here. Instead, I will sumarize the more interesting and saliant points that are easier to understand. The most important thing to remember is the role the valves play in the proper flow and passage of CSF from the subarachnoid spaces to the venous drainage system of the brain.
Because of the critical role they play in flow, these special valves also affect CSF volume and pressure in the brain. Therefore, understanding the role of the arachnoid granulations is essential to the treatment and prevention of hydrocephalus. The arachnoid granulations are depicted in green in the picture and protrude from the subaracnoid space (green) into the superior sagittal sinus (blue).
Hydrocephalus, CSF Shunts and Valves
The image below of a hydrocephalus case was contributed to Wikipedia by Lucien Monfils, a radiology technician from the Netherlands. Hydrocephalus is a condition in which the volume of CSF in the brain increases. CSF is produced in the ventricles and increases in CSF volume causes the ventricles to enlarge as in the picture below, which is called hydrocephalus. When the ventricles enlarge they compress the brain.
Hydrocephalus is typically thought of as a childhood condition caused by excess CSF production or blockage of its pathways. Blockage of its pathways prevents CSF from exiting the brain and skull which increases volume. In children the increase in volume causes the head to enlarge. The current treatment for childhood hydrocephalus is to use a cerebral shunt to drain excess CSF volume. Cerebral shunts use a tube surgically inserted into the ventricles of the brain that removes and reroutes CSF to different parts of the body, such as the abdomen where it is called a peritoneal shunt.
The key component to successful cerebral shunts is the different types of CSF valves and other means they use to control CSF volume. CSF shunts and valves have come a long way since their introdution back in 1955. Nonetheless, the technically more advanced shunts and special valves still haven’t entirely solved the problem. What’s more, they can cause other problems. One of the major problems is over drainage, which can cause conditions such as pressure conus and Chiari 1 type malformations. A pressure conus or Chiar 1 malformation occurs when the brainstem sinks slightly (3-5mm) into the foramen magnum. This can cause dizziness, nausea and headaches among other things. Shunts can also shift out of place and cause problems or they can become blocked with debris, such as from proteins found in the blood.
The biggest problem with shunts, however, has to do with siphoning. Siphoning causes problems similar to over drainage in which too much CSF is removed from the brain. As stated above, this causes the brain to sink into the foramen magnum, which is called a pressure conus or Chiari 1 malformation. The biggest challenge shunts must contend with to prevent siphoning is when a patient changes positions from lying down to standing upright. Standing upright causes sudden drainage of CSF from the brain that takes time to recover. Similar challenging postional pressure fluctuations in the body and brain occur during coughing and straining, such as in lifting a heavy object, can cause back pressure against the brain.
In contrast to enlarged ventricles as seen in the hydrocephalus case above, over drainage of CSF causes it to accumulate in the extra axial spaces. The extra axial spaces are the subarachnoid spaces that surround the brain which contain CSF. In severe cases over drainage can cause slit ventricles in which the brain compesses the ventricles down to mere slits. In either case, the brain gets compressed by an increase in CSF volume in its core inside the ventricles, or by an increase in CSF volume outside the ventricles in the spaces that surround the brain. I will cover more on hydrocephalus, cerebral shunts and CSF valves as this site develops. Suffice it to say, valves are critical to CSF flow, volume and pressure.
Understanding hydrocephalus is important because in addition to children, it also affects adults. In adults it is called normal pressure hydrocephalus. In contrast to children, in normal pressure hydrocephalus CSF pressure remains normal or just slightly elevated. Normal pressure hydrocephalus (NPH) may play a much more significant role in the cause of neurodegenerative diseases such as, Alzheimer’s, Parkinson’s and multiple sclerosis, than we currently realize. I discuss this in depth in my book “The Downside of Upright Posture”. Humans are predisposed to hydrocephalus due to the unique design of the skull, spine and circulatory system of the brain as a result of upright posture.
CSF Pulsations and Pressure Gradients
For CSF to flow properly there must be a sufficient pressure gradient. In other words, like water, CSF flows from a point of higher pressure to a point of lower pressure. Proper CSF flow also relies on pulsations, which form waves. What’s more, arterial pulsations and vascular pressure gradients also affect the performance of the CSF valves in the arachnoid villi.
The pressure gradient for CSF flow is determined by the difference in pressure in the ventricles where it is produced and the pressure in the dural sinuses where it enters the venous drainage system of the brain. Intracranial pressure (ICP) is a measurement of pressure in the ventricles.
Most of the CSF passes through arachnoid granulations (villi) as it leaves the subarachnoid space and empties into the superior sagittal sinus at the top of the brain. That makes the superior sagittal sinus venous pressure (SSVP) the low side of the CSF pressure gradient.
The flow of venous blood in the dural sinues is, likewise, determined by a pressure gradient. That pressure gradient is determined by the difference in pressure between the superior sagittal sinus and the internal jugular and vertebral veins of the accessory drainage system of the brain.
The pulsations that drive CSF come from the beating of the heart transmitted through the arterial system of the brain. The waves are further amplified by changes in respiratory pressure inside the chest cavity (thorax). Exhalation increases pressure on the arteries and veins of the heart and lungs which is transmitted to the brain.
Declining circulation that comes with age reduces the pulsations or waves that drive CSF flow thus causing the stream to slow down. Because of its connection to the dural sinuses, obstruction to the drainage system of the brain such as chronic cerebrospinal venous insufficiency (CCSVI) or chronic craniocervical venous back pressure (CCVBP) can further affect CSF flow by decreasing its pressure gradient. The combined affect can cause CSF flow to get sluggish and CSF volume start to increase in the brain.
One of the keys to solving neurodegenerative processes and subsequent diseases such as Alzheimer’s, Parkinson’s and multiple sclerosis will be understanding CSF flow. As mentioned above, an increase in CSF volume can cause hydrocephalus. On the other hand, a decrease in CSF production could lead to a pressure conus or Chiari 1 type condition. The proper production, volume, flow and removal of CSF is essential to the health of the brain and cord.