Certainly, the most important function of the skull is to protect the fragile brain, lying within the cranial cavity. As Figure 1-6 indicates, the skull is well-designed for the job. If we cut through the calvarium in the plane shown in A and look down from above we get view B. The contour of the brain's surface matches that of the cranial cavity rather well, but there is a small space between the two. This narrow gap, shown by green stippling in the figure, is called the subarachnoid space. It is filled with cerebrospinal fluid (CSF) and also contains three membranes known collectively as the meninges. The brain is, in a sense, floating in CSF which protects it from "bumping into" the skull during sudden movements of the head. From a clinical point of view, the anatomy of this region is extremely important and we want to look at it in detail. The best way to start is to consider CSF - where does this fluid come from, how does it get into the subarachnoid space, where is it going, and how does all this relate to the meninges? To come up with the answers, we will jump around a bit. First, let's look at a few views taken from an old lecture on brain development.

BRAIN DEVELOPMENT

The first old lecture figure, Dev-1, shows that the central nervous system develops from a flat sheet of ectoderm. In the first few days following fertilization of the ovum, the single celled zygote divides repeatedly to form a solid cell mass of 12 - 16 cells called a morula. During the second week of development this structure implants in the wall of the uterus. Two cavities now develop within the mass - the amnionic cavity above and the yolk sac below. Between these two lies the embryonic bilaminar disc, consisting of a layer of ectoderm lying above a layer of entoderm. During the third week of development a region termed the primitive streak forms on the dorsal surface of the disc, giving a longitudinal axis to the developing embryo. Cells from the surface of the disc migrate through this region and then spread out between the ectoderm and the entoderm to create a new cell layer. The cells that migrate laterally form mesoderm, thus transforming the bilaminar disc into a trilaminar one. Other cells migrate anteriorly in the midline to form the notocord. By a process of neural transduction, the notocord induces the overlying ectoderm to become neural tissue - the neural plate. In the midline, just above the notocord, a neural groove forms. Lateral to this on either there is a proliferation of neural ectoderm to form neural folds.

In figure Dev-2 we see that the flat sheet of ectoderm rolls up to form a tube. On about day 18 following fertilization, the process of neurulation begins. Starting in the cervical region, the neural folds migrate dorsally and fold toward the midline to meet and fuse, forming the first part of the neural tube. Fusion of the folds then extends both rostrally and caudally. For several days the ends of the neural tube remain open, so that the central canal is in communication with the amnionic cavity. The rostral opening, or cranial neuropore, is closed at about day 25 by a membrane called the lamina terminalis. The caudal neuropore closes a few days later. Failure of the cranial neuropore to close leads to anencephaly, a developmental defect which grossly distorts the development of the brain. Failure of the caudal neuropore to close is associated with some form of spina bifida.

Some tissue of the neural plate fails to become incorporated in the neural tube and remains just dorsolateral to it. This neural crest tissue ultimately gives rise to many structures, including: 1) the dorsal root (sensory) ganglia of the peripheral nervous system; 2) the ganglia of the autonomic nervous system; 3) the cells of the adrenal medulla and 4) the Schwann Cells that form the myelin that surrounds peripheral nerves. Lateral to the neural tube the mesoderm becomes organized in a segmental fashion into somites which will, ultimately, impose a segmental pattern upon the peripheral nervous system.

In the normal central nervous system the two edges of the neural folds fuse in most regions, so that nervous tissue surrounds a central cavity. In the case of the rostral ("upper part") neural tube, some parts of the central cavity dilate to form vesicles (Dev-3), which will persist as ventricles in the adult brain. (Dev- 4) shows that by the fifth week of development the lateral wall of the prosencephalon has pushed outward in a blister-like manner, carrying the central cavity with it to form a new space called the lateral ventricle. The part of the cavity that remains behind, in the mid-line, becomes the third ventricle. There is also a less than obvious subdivision of the space within the rhomencephalon, forming the rostral and caudal parts of the fourth ventricle.

Thus, we now have 5 cavities within the brain:

• 1) The lateral ventricle
• 2) The third ventricle
• 3) The cerebral aqueduct
• 4) The rostral fourth ventricle
• 5) The caudal fourth ventricle

These spaces will form the ventricular system of the adult brain, and as we shall see in the next view, Figure 1-8, the tissue that is the wall of each space becomes a major subdivision of the adult brain. Rostrally (i.e., at the very "top" of the neural tube) the lamina terminalis seals the ventricular system closed.

However, as Figure 1-7 illustrates, in some regions the edges of the neural plate fail to meet, even in the normal brain. In these instances , the ependymal cell layer, lining the cavity, and the layer of pial cells, covering the surface of the tube, meet to form a membrane which completes closure of the cavity. Blood vessels extend into this membrane creating highly vascular tissue called choroid plexus. The two regions where this occurs are shown in the highly schematic figure Dev-8. In A, which is simply a restatement of Figure 7, we see the situation in the medulla. In B, which is a restatement of Figure 8, we see that the edges of the neural tube also fail to meet at the level of the diencephalon. Thus both the third and fourth ventricles are roofed by choroid plexus. Furthermore the choroid plexus of the third ventricle is carried out into the lateral ventricles within the hemisphere. Choroid plexus tissue is the main source of CSF, and since the greatest mass of this tissue is found lining the two lateral ventricles this is where most CSF is produced. For a 3D view of the choroid plexus, see DiganatA_16A8 .

This brief description of brain development is adequate for our purposes, but if you would like a somewhat more detailed story, try Tantorski's Unit 1.

THE FORMATION AND FLOW OF CSF

Now, let's look at a series of slightly more realistic frontal sections through the skull and brain. The first view, Figure 1-9, traces the flow of CSF. From the major site of formation, in the two lateral ventricle, fluid passes through the interventricular foramen to enter the third ventricle. A bit more fluid comes from the choroid plexus roofing the third ventricle; CSF exits into the cerebral aqueduct and descends into the fourth ventricle. Again, choroid plexus in the roof of this ventricle contributes a small amount of CSF to the total. CSF exits from the ventricular system through paired lateral openings, the Foramina of Luschka, and a single midline opening in the roof of the ventricle, the Foramen of Magendie. Once outside, the fluid lies within the subarachnoid space - a region defined more precisely in a coming view. For now, just trace the arrows up over the surface of the brain to the arachnoid granulation (Figure 1-12). CSF enters these specialized structures and from here returns to the venous blood of the superior sagittal sinus. For fun, look at this You Tube short video.

Diagrams of choroid plexus tissue (Blumenfeld Fig. 5-13, Haines Fig. 6-18) show that the fenestrated capillaries within choroid tissue allow for free passage of water and solutes but that tight junctions between choroid epithelial cells form a blood-CSF barrier. While lipid soluble substance may easily pass through this barrier, most other materials must be conveyed from blood to CSF by active transport through cells of the choroid epithelium. The result is that the chemical composition of the two fluids differ; for example, CSF has higher levels of chloride, magnesium and sodium, compared with plasma. CSF is colorless, low in protein and contains very few, if any, white blood cells.

The volume of CSF in the adult is about 120mL and roughly 500mL of the fluid is produced every day, so that about 4 turnovers occur in 24 hour. Production continues even if there is a blockage of flow, somewhere along the way to the arachnoid granulations, but the result depends on the age of the subject and the site of the obstruction. For details, see Blumenfeld, pages 151-2, Haines, pg. 101.

Most CSF returns to the vascular system by entering arachnoid granulations. Some fluid passes between the cells lining a granulation to mix with the venous blood of the superior sagittal sinus. Most of the CSF, however, is transported through the cells in membrane bound vesicles. Granulations are easily seen in gross specimens. If the dura is carefully removed from the surface of the brain, they tend to pop out of the superior sagittal sinus and be exposed to view, as in Figure 1-13. Another approach is to open the superior sagittal sinus in the midline and look at the granulations as they protrude into the sinus (Figure 1-14).

MENINGES - THE DURA

Clearly, there is an intimate relationship between CSF and the meninges so let's consider these tissues next. The outermost of the three layers is the dura - short for dura mater. It is a tough, fibrous layer, having the feeling and strength of canvas. Figure 1-10 shows a piece of it, lying on the surface of the brain. As shown in Figure 1-11, the dura consists of an outer periosteal layer, which is tightly adherent to the skull, and an inner meningeal layer. In most regions the two layers appear fused into a single one, and some textbooks describe it that way. Important features regarding the dura are:

• 1) In some regions the meningeal layer of the dura breaks away from the dural one to form tough, unyielding folds or partitions which partially subdivide the cranial cavity. Two of these - the falx cerebri and the tentorium cerebelli- are shown in several figures and labeled in Figure 15. The falx cerebri, and its posterior extension, the falx cerebelli, is also shown in Figure 16. These partitions are important because when expanding lesions in the cranial cavity - blood or a tumor - displace brain tissue, it is often obliged to herniate around one of them. For a discussion of these herniation syndromes see Blumenfeld, pg. 140, Haines pg. 111. For a look at the falx cerebri and tentorium cerebelli in a dissected specimen, see DiganatA_1.13 .
• 2) When the dural layers separate, as described above, they often enclose a network of venous sinuses. This is shown most clearly in Figure 15, where the superior sagittal sinus. the inferior sagittal sinus and the superior petrosal sinus are labeled. Another example, in which the meningeal dura encloses a sinus, is the straight sinus (Figure 16). In this case, the sinus is created in the region where the falx cerebri joins the ridge line of the tentorium cerebelli. See Haines, pgs.110-112 for more diagrams and details. The transverse and sigmoid sinuses are so large that they erode depressions in the overlying bone (Figure 1-3, Figure 1-4).
• 3) The layers of the dura also split to enclose the middle meningeal artery. The split is asymmetrical in that the meningeal surface - the one that the brain rubs against when it moves slightly within the cranial cavity - remains smooth, but the vessel creates a ridge in the periostial surface. This is shown clearly in shown in Figure 17. The specimen of dura shown in Figure 10 was subsequently removed from the surface of the brain and cut into these two pieces. Then india ink was injected into the middle meningeal artery. Note how the branches of the vessel stand out on the outer ( = periosteal ) surface. If you rubbed your finger over it, you would easily feel these ridges. In contrast, the inner ( = meningeal ) surface is quite smooth. When the brain moves slightly within the skull (when you bump your head against a wall, for example) the brain's surface moves, relative to the inner surface of the dura, and it makes sense for the latter to be smooth.The result of this asymmetrical split is that the artery erodes a "valley" in the inner surface of the skull., as shown in Figure 18. If the skull fracture and the fracture line crosses this valley, then there is a good chance the middle meningeal artery will be torn and that arterial blood will leak forming a hematoma (pool of blood) between the dura and the skull. We discuss this problem in great detail below.
• 4) The dura is a pain-sensitive structure - but the arachnoid, pia and the brain itself are not. The dura of the anterior and middle fossae receives sensory endings from the trigeminal nerve (Figure 1-21). The dura of posterior cranial fossa is supplied by branches of the vagus nerve, coming off before it exits from the cranial cavity) and by branches of spinal nerves C2 and C3, that enter through the Foramen Magnum. The significance of this is that irritation of the dura may be perceived (or "referred" to) as coming from sensory territory of the trigeminal or upper cervical nerves.
• 5) At the Foramen Magnum the periostial and meningeal layers of the dura part ways. The periostial layer continues on to the external surface of the skull, while the meningeal layer forms a tube, hanging rather freely within the vertebral canal, enclosing the spinal cord (Figure 19, Figure 20). Since the cranial dura is tightly adherent to the skull, there is - normally - no epidural space in the cranial cavity. In contrast, there is a true spinal epidural space and, as Figure 1-19 shows, it is filled with fatty tissue and a plexus of veins. The venous plexus, known as Batson's plexus, is important because it extends the length of the vertebral canal and the veins have no valves, allowing blood flow in either direction. This forms an important route by which prostatic cancer cell may easily spread to vertebrae.
• 6) The dura forms a pressure tight seal around everything that passes through it - blood vessels and nerves - with the result that the pressure within the cranial cavity and spinal dural sleeve differs from atmospheric pressure. This is shown schematically, for exiting spinal nerves, in Figure 19. For a description of how this pressure is measured, see Blumenfeld, pgs. 161-2.

MENINGES - THE ARACHNOID AND PIA

Deep to the dura lies the arachnoid, a delicate membrane that is easily separated from the dura in most places, but pressed tightly against it by the pressure of the CSF lying in contact with it's inner surface. The third meningeal layer is the pia, a fine cellular layer which is adherent to the surface of the brain. As Figure 1-11 shows, the pia dips into the complex sulci and fissures that characterize the surface of the hemisphere, whereas the arachnoid does not. Since these two membranes form the borders of the subarachnoid space, small pools of CSF accumulate in these regions. Figure 1-13 shows this in a brain specimen in which the dura has been removed. In this case, there is no CSF to lift the arachnoid off the brain; a needle has been use to make a tear in the arachnoid and expose the "spider web like" filaments that pass between arachnoid and pia (and are not shown in our drawings).

In most regions the pia and arachnoid are separated by only a few mm, but in some places the gap becomes much larger and accumulations of CSF, termed cisterns, are formed in the expanded subarachnoid space. Sometimes this happens because the arachnoid fails to follow the pia into cul de sacs formed by the brain's surface; the cisterna magna, quadrigeminal cistern and interpeduncular cistern are good examples (Figure 22). Another cistern, the prepontine one, occurs because the large basilar artery, running in the subarachnoid space, pushes the arachnoid and pia apart, as suggested in Figure 1-16. For more about cisterns see Blumenfeld Pages 132-3, Haines Page 118 and Figure 7-17.

THE MENINGEAL SPACES AND INTRACRANIAL BLEEDING

The meninges, by their very existence, define three clinically important spaces.

• 1) The epidural space is a potential one because the dura normally lies in direct contact with the inner surface of the skull. However, when skull fractures occur and the fracture line crosses the valley which the middle meningeal artery erodes in the skull then there is a good chance that the vessel will be torn. If this happens, the position of the artery is such (Figure 18) that blood will force its way between the dura and the skull, creating an epidural hematoma. Because the dura is adherent to the skull, the accumulating mass assume a characteristic "lens" shape as blood dissects the dura away from the skull (see Blumenfeld Pages. 178-9 for a typical lesion). Take a look at the You Tube video
• 2) The subdural space lies between the dura and the arachnoid and is also only a potential one, since the pressure of CSF normally presses the arachnoid against the dura. However if, in an accident, the skull strikes a hard surface (the dashboard of a car), the brain may shift position slightly within the cranial cavity and as a result the bridging veins, passing from the surface of the hemisphere into the superior sagittal sinus (Figure 12) may be torn. These veins pass through the subdural space, and that's where the blood accumulates. Since the the dura and arachnoid easily separate, the blood in this case spreads easily over the surface of the hemisphere (see Blumenfeld pg 166 for a typical lesion). Take a look at the You Tube video.
• 3) The subarachnoid space is, of course, a real one, normally filled with CSF, but the arteries supplying the brain run in this space. When one ruptures, blood escapes into the space and spreads diffusely.