Cerebral Meninges, CSF and the Blood-Brain Barrier

Question 1

What are the bones containing the brain called? What about the bones underlying the face and jaw?

Answer 1

• The bones of the skull that contain the brain are called the cranial bones or cranium (sometimes neurocranium); those that underly the face and jaw are the facial skeleton.

Question 2

What are the four cranial bones? What is the space within them called?

Answer 2

Cranial bones are the frontal, parietal, occipital and temporal bones. The region under each cranial bone is called a cranial fossa.

Question 3

What do the cerebral meninges consist of?

Answer 3

• Consist of three membranes:
  o 1) Dura is adjacent to skull & attached to bones of cranium. It has two layers, an outer and periosteal layer and an inner meningeal layer, which are fused together
  o 2) Arachnoid has outer compact layer of ‘barrier’ cells
  o and inner ‘trabecular’ meshwork containing cerebrospinal fluid (CSF)
  o 3) Pia is a thin membrane tightly attached to basement lamina of brain

Dura = hard
Arachnoid = spiders web
Pia = close, tight

Question 4

What is the blood supply to the meninges?

Answer 4

• Blood vessels are found within the dura
• Some veins cross the dura-arachnoid interface.
• Many blood vessels are found in the subarachnoid space, which contains connective tissue ‘trabeculae’ and is filled with CSF

Question 5

What does the cerebrum consist of? How is it divided? Where is it located?

Answer 5

• The cerebrum consists of the cerebral cortex and underlying deep structures above the cerebellum*. It is divided into regions (lobes) that fit in the corresponding cranial fossa. The frontal lobe lies under the frontal bone in the anterior cranial fossa, the temporal lobe lies under the temporal bone in the middle cranial fossa and the occipital lobe lies under the occipital bone in the posterior cranial fossa, along with the cerebellum. The parietal lobe lies under the parietal bone.
• *The cerebellum is another but simpler cortical structure that is part of the hindbrain

Question 6

What are gyri and sulci? What are the two main sulci known as and where are they located?

Answer 6

• The outwardly rounded ridges of cortex are GYRI (singular GYRUS)
• The grooves between the gyri are SULCI (singular SULCUS)
• The two main sulci are also known as fissures. These are the central sulcus (fissure) between the frontal and parietal lobes, and the lateral sulcus (fissure) between the frontal and temporal lobes

Question 7

What is hidden inside the lateral fissure?

Answer 7

The insula

Question 8

What are the transverse sheets of dura called?

Answer 8

Tentorium cerebelli

Question 9

What is the dura like? What is exposed when it is pulled back?

Answer 9

Tough and leathery

Exposes arachnoid and underlying brain

Question 10

What does the dura form as it continues down in the space between the hemispheres? What does this structure form at the occipital pole?

Answer 10

Falx (falx cerebri)

Forms a ‘t-junction’ with occipital dura at the occipital pole

Question 11

What are cisterns? What are four examples of these?

Answer 11

• There are places around the brainstem where the subarachnoid space is enlarged due to the curvature of the brain surface. These places are called cisterns.
  Superior cistern, cistern magna, pontine cistern and interpeduncular cistern.
  See diagram on lecture notes for locations

Question 12

What are the 4 forms of cerebral haemorrhage?

Answer 12

1. Bleeding between skull and dura
2. Bleeding between dura and arachnoid
3. Bleeding in subarachnoid space
4. Intracerebral haemorrhage

Question 13

What are the causes, symptoms and treatments for bleeding between the skull and dura?

Answer 13

o This is an epidural haemorrhage ; usually arterial. May be no symptoms at first then (minutes/hours later) severe headache as haematoma compresses brain. Epidural haemorrhage is usually arterial therefore rapidly increasing in size. Lens shaped in MRI. Usual cause is acute skull trauma. Patients may regain consciousness during what is called a lucid interval, only to descend suddenly and rapidly into unconsciousness later.
o The lucid interval, which depends on the extent of the injury, is a key to diagnosing epidural hemorrhage. If the patient is not treated with prompt surgical intervention, death is likely to follow due to compression of brain and herniation.

See MRI images in lecture notes

Question 14

What are the causes, symptoms and characteristics of bleeding between the dura and arachnoid?

Answer 14

o This is a subdural haemorrhage: due to tearing of veins bridging between dura and arachnoid. A venous bleed therefore onset of symptoms slow, (24 hours) imaging shows blood spread diffusely over brain surface.
o The blood spreads slowly across the brain surface forcing a gap between dura and arachnoid. Imaging shows blood spread diffusely over brain surface. Although not as rapid as an epidural bleed, an untreated subdural bleed can be fatal as it gradually compresses the brain. MRI is crescent shaped.

See MRI images in lecture notes

Question 15

What are the causes and symptoms of bleeding in the subarachnoid space?

Answer 15

3. Bleeding in subarachnoid space: this is a subarachnoid haemorrhage often from ruptured aneurysm of arachnoid artery; : symptoms sudden severe headache ‘thunderclap headache’: a form of stroke

Question 16

What are the causes of an intracerebral haemorrhage?

Answer 16

4. Intracerebral haemorrhage; due to a ruptured artery inside the brain (e.g. a branch of middle cerebral artery. A classic stroke.

See diagram in lecture notes for location of each type of haemorrhage.

Question 17

What are cerebral ventricles? What are the names of the four ventricles? What are they filled with, and what are they lined by?

Answer 17

• The cerebral ventricles are fluid filled spaces in the brain.
• Cerebrospinal fluid (CSF) is made in and fills the cerebral ventricles.
• There are four ventricles:
  o The lateral ventricles (1&2)
  o The third ventricle
  o The fourth ventricle
• The ventricles are lined by a form of connective tissue called ependymal cells

See diagrams and MRIs in lecture notes for locations

Question 18

In a T2 weighted image, what colour is water?

Answer 18

White

Question 19

What and where is the choroid plexus, and how does it form cerebrospinal fluid? What are the characteristics of choroid capillaries? How much CSF is made per day?

Answer 19

• Cerebrospinal fluid is formed by the choroid plexus, a meshwork of capillaries covered by ependymal cells protruding into the ventricles of the brain.
• There is choroid plexus in all the ventricles, but the majority is in the lateral ventricles. Choroid plexus capillaries are somewhat similar to glomeruli in kidneys; both produce a nearly protein-free filtrate from blood. (CSF contains approximately 0.3% plasma proteins).
• Choroid capillaries are fenestrated: an ultrafiltrate of blood passes through the capillary fenestrations into the subependymal layer. Gaps between ependymal cells regulate the flow of CSF to approx 500 ml/day.

See diagram in lecture notes

Question 20

What is the brain largely composed of? What property does this give it? What pathologies can this result in?

Answer 20

• The brain tissue is largely composed of lipid (in cell membranes and myelin) which is less dense than water. Hence the brain ‘floats’ in the cerebrospinal fluid, its movement limited by the falx and tentoria, and anchored by the cranial nerves. Trauma can make the brain ‘bounce’ against the dura, causing contusions (bruising) on the cortical surface.

Question 21

What is the function of cerebrospinal fluid? What does it contain? How is it pH buffered? At what rate is it produced per day? How much CSF does the brain hold? How much glucose does CSF contain? What pressure is CSF at, and what causes this to change?

Answer 21

• Acts as hydrostatic support and shock absorber for brain. The CSF contains approximately 0.3-1.0 % plasma proteins, (measured by lumbar puncture), about 1/100 of the concentration in plasma.
• Because cerebrospinal fluid contains very little protein & no cells it is not pH buffered in the same way as blood: small changes in pCO2 in blood cause appreciable changes in csf pH.
• The cerebrospinal fluid is produced at a rate of 500 ml/day.
• The brain holds from 135-150 ml csf
• CSF contains about 60% of the glucose concentration of plasma. Glucose is transported through capillary endothelium by facilitated diffusion mediated by glucose transporter proteins.
• CSF pressure ranges from 4.4 - 7.3 mmHg (0.6-0.9 kPa), with most variations due to coughing or internal compression of jugular veins in the neck.

Question 22

Where does CSF flow from/to? In what direction does it flow? Where is it absorbed and where does it go afterwards?

Answer 22

• CSF flows from lateral ventricles to third ventricle to fourth ventricle to cisterna magna. Here it passes out through the median aperture (aka foramen of Magendie) into the cisterna magna. It then flows upwards over the cerebral cortex in the subarachnoid space to the area around the falx. Then is absorbed in arachnoid granulations in the superior sagittal sinus and joins the venous blood in the superior sagittal sinus

See diagram in lecture notes for exact path

Question 23

What are arachnoid granulations and where are they located?

Answer 23

• Arachnoid granulations are protrusion of the arachnoid that penetrate the dura at the top of the brain and enable cerebrospinal fluid to drain into the superior sagittal sinus, which is a kind of vein that runs sagittally along the midline between the two layers of the dura.

Question 24

What is hydrocephalus? What does it result from? How is it treated? What is the prognosis? How is it protected?

Answer 24

• Is an accumulation of cerebrospinal fluid (CSF) in the ventricular system. With the exception of overproduction of CSF by a rare papilloma of the choroid plexus, hydrocephalus results from obstruction of the normal CSF circulation, with consequent dilatation of the ventricles. Usually due to blockage in cerebral aqueduct. Repaired by shunt (tube inserted in third ventricle leading to subarachnoid space) Prognosis good if done early. Detected by translucent skull (no brain matter to block light)

Question 25

What are glial cells? What do they control to allow for action potential production of nerve cells? How do they help with energy metabolism of neurons? What else are they required for? What pathologies do they cause and how?

Answer 25

- The majority of cells in the central nervous system are not neurons; the ‘support’ cells of the brain are called glia or glial cells and these cells outnumber the neurons. - Action potential production of nerve cells requires glial cells as they control the extracellular concentrations of sodium and potassium ions. - Energy metabolism of neurons requires glia to provide glucose and/or lactate - Myelination of neurons requires glial cells - Epilepsy is often caused by a malfunction of the glial cells in a region where an infarct or other neuronal ‘insult’ (contusion, impact, infection) has occurred. - Most tumours of the brain are gliomas. This is because neurons cannot divide (undego mitosis). The cellular machinery that normal cells use for mitosis in neurons is used to produce the long processes of axons and dendrites that are characteristic of nerve cells.

Question 26

What are the four main types of glial cell and what do they do?

Answer 26

o Astrocytes  Astrocytes are so named because they have a ‘star-shaped’ appearance with lots of processes like dendrites; several different forms exist. (Like neurons but without axons). o Oligodendrocytes  Oligodendrocytes are the CNS equivalent of Schwann cells: they make myelin for CNS axons. o Ependymal cells  Ependymal cells line the ventricles and choroid plexus; they control the production of CSF o Microglia

Question 27

What are astrocytes and how can they vary in form? What are their functions? What pathology can they cause and why?

Answer 27

- Astrocytes are like ‘personal assistants’ or ‘butlers’ for neurons. They vary in form between gray matter (protoplasmic astrocytes) and white matter (fibrous astrocytes). - Functions o Astrocytes maintain local pH and glucose in the correct range, and remove excess neurotransmitters from synapses. o Astrocytes maintain correct electrolyte levels around neurons; in particular, they prevent extracellular potassium build up (which can cause siezures) o Astrocytes secrete growth factors vital to the support of some neurons. In disease processes, astrocytes may secrete cytokines, which regulate the function of immune cells invading CNS tissue. o If injury to the CNS results in cell loss, the space created by the breakdown of debris is filled by proliferation and/or hypertrophy of astrocytes, resulting in the formation of an astrocytic scar. - Astrocytes (unlike neurons) continue to divide and multiply in the brain during life. Most brain tumours are astrocytomas

Question 28

What are microglia and what percentage of brain cells do they account for? How do they carry out their immune role? What have recent studies shown them to have a role in? What pathologies can they contribute to?

Answer 28

- The blood-born immune cells such as neutrophils, lymphocytes etc cannot get into the brain due to the blood-brain barrier. Microglia are a form of glial cell that act as resident macrophages in the brain. Microglia account for 10–15% of all cells found within the brain. - As the resident macrophages, they act as the first and main form of active immune defense in the central nervous system (CNS). They are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents such as bacteria or fungi. - Recent work shows microglia have a role in promoting axonal outgrowth in the fetus and after nerve injury. They also have a role in ‘synaptic pruning’ie removal of unwanted or unnecessary synapses. - Ageing microglia that no longer operate effectively may be a key factor in the development of neurodegenerative diseases such as Alzheimer’s.

Question 29

What are astrocyte end-feet? What do they cover? What is their function in the capillaries?

Answer 29

- The processes of astrocytes end in expansions called end feet. Most of the free surface of neuronal dendrites and cell bodies, are covered with apposed astrocyte end feet. - Similarly, every blood vessel in the CNS is jacketed by a layer of end feet - One function of the capillary end feet is to regulate uptake of glucose from blood into brain. At least some of the glucose is converted to lactate which is transferred into neurons which can convert it to pyruvate to use in the tricarboxylic acid cycle - Astrocyte end feet also regulate uptake of amino acids, with separate transporters for acid, neutral and basic amino acids a. End-feet around capillaries take up glucose from blood for use by neurons to make ATP; converted first to lactic acid b. Store glycogen and produce lactate for neurons to use

Question 30

What is the Blood-Brain barrier and what forms it? What features does it have to prevent exit of materials not regulated by astrocytes? What substance is NOT the blood-brain barrier NOT a barrier to?

Answer 30

- The combination of astrocyte end-feet and endothelial tight junctions make up the Blood-Brain Barrier - Brain capillaries have tight junctions between the endothelial cells that prevent exit of materials not regulated by astrocytes - The blood -brain barrier is NOT a barrier to lipid soluble molecules, and many lipid-soluble molecules can cross the blood-brain barrier unaided. For example, opiates such as diacetylmorpine (heroin) can cross the BBB and so rapidly reach brain cells after IV injection. See diagram in lecture notes

Question 31

Why does the blood-brain barrier have such clinical significance? What happens to it in certain pathological conditions? Why can this be useful?

Answer 31

- The blood-brain barrier has considerable clinical significance. As a barrier, it normally prevents many drugs, such as most antibiotics, from reaching the brain. The exclusion of antibiotics from the brain seriously complicates the management of CNS infections. - The blood-brain barrier breaks down in certain pathological conditions. This can be useful. For example, in meningitis the meningeal inflammation breaks down the barrier and this enables penicillin to penetrate the brain tissue.

Question 32

What might cause the blood-brain barrier to break down?

Answer 32

Hypertension (opens the BBB) Development (BBB not fully formed at birth) Hyperosmility (a high concentration of a substance in the blood can open the BBB) Microwaves (exposure can open the BBB) Radiation (exposure can open the BBB) Infection (exposure to infectious agents can open the BBB) Trauma, Ischaemia, Inflammation, Pressure (injury to the brain can open the BBB)