Blood brain barrier

Question 1

What are the four main systems which are involved in the protection and nourishment of the brain?

Answer 1

Skull and vertebral column
Meninges and protective membrane
Cerebrospinal fluid
Blood brain barrier

Question 2

What is the vertebral column?

Answer 2

Also known as the spinal column it consists of vertebrae which stretch from the skull to the pelvis. Essentially acts to protect the spinal cord.

Question 3

What are the meninges?

Answer 3

They are meninges that enclose the brain and spinal cord. Importantly meninges are not the blood brain barrier. The meninges coat not only the brain but also extended and cover the spinal cord.

Question 4

Describe the different layers of the meninges.

Answer 4

Meninges consist of three layers:
Dura mater which sits below the cranium (skull) in addition to the spinal cord- which is a tough, strong outer membrane
Arachnoid mater- highly vascular, spiders web like layer
Pia mater - the inner layer which adheres to the membrane tissue

Question 5

Where are two layers of the dura mater found?

Answer 5

In the brain the dura mater membrane consists of two layers, one of which sits below the cranium and the other covering the brain membrane. The area between these membranes is known as the dural sinus which is filled with blood.

Question 6

What is the importance of maintaining the extracellular compartments?

Answer 6

Neurons are very sensitive to any changes in their extracellular environment such as changes in their electrolyte concentrations and neurotransmitters as it can cause changes to their neuronal function. Therefore it must be remained constant such as potassium, glycine and glutamate levels.

Question 7

What are the two main extracellular compartments?

Answer 7

This includes both the cerebrospinal fluid (ventricles and central canal of the spinal cord) and the interstitial compartment which is the interstitial fluid around the CNS cells.
There is ongoing exchange between the two extracellular compartments and then the interstitial compartment with the intracellular compartment with the neurons and therefore both must be maintained at a constant level.

Question 8

What are the ventricles, what do they contain?

Answer 8

They are cavities within the brain which are filled with cerebrospinal fluid.

Question 9

Where are the ventricles located within the brain?

Answer 9

There are four ventricles within the brain, two lateral ventricles located, one on each cerebral hemisphere. These drain into the third ventricle in which the diencephalon is centered around that sits between the two cerebral hemispheres and the fourth ventricle that sits in the brain stem which the third ventricle drains into and is continuous with the central canal of the spinal cord.

Question 10

What are the ventricles lined with?

Answer 10

Ciliated ependymal cells and it is the beating of the cilia which enables the movement/circulation of the CSF around the ventricles.

Question 11

Are the ciliated ependymal cells responsible for the secretion of cerebrospinal fluid?

Answer 11

No, they simply aid its circulation within ventricles. It is secreted by the choroid epithelial cells of the ventricles, which facilitate the turnover of the CSF. The choroid plexus (bundle of cells) is found for each of the ventricles producing the CSF.
The fine balance between the secretion, composition, volume and turnover of cerebrospinal fluid (CSF) is strictly regulated to ensure constant pressure.

Question 12

Which conditions may have a raised intracerebral pressure?

Answer 12

Hydrocephalus, idiopathic intracranial hypertension, brain trauma, brain tumours and stroke can all experience a raised intracerebral pressure which can be life-threatening when there is distributed cerebrospinal fluid circulation.

Question 13

What is the volume of the CSF and how regularly is it turned over?

Answer 13

CSF is produced at a rate of around 500 ml/day; there are estimates that there is approximately 125 mL to 150 mL of CSF in the body at any given time. It is completely turned over roughly every 7.5 hours.

Question 14

How does the contents within the CSF differ from that in the blood?

Answer 14

Less potassium, more sodium and no protein; its composition is tightly controlled.

Question 15

What is the main purpose of the CSF?

Answer 15

As the same density as the brain tissue itself it allows the brain to float on it acting as a shock absorber cushioning the brain against the skull.

Question 16

How is the CSF removed as part of the turnover process?

Answer 16

The drainage point is within the fourth ventricle and it drains into the subarachnoid space (the space between the arachnoid layer and the pia mater). It circulates around the brain before exiting then via the arachnoid villi through the dura mater into the dural sinus (the layer between the two dura mater membranes) which is filled with blood, in the venous system.

Question 17

What is the blood brain barrier a barrier between?

Answer 17

It is a barrier between the blood and the interstitial fluid.

Question 18

What is the BBB formed of?

Answer 18

Cerebral microvascular endothelial cells and the associated cells/structures with a huge barrier.

Question 19

What is the importance of the BBB?

Answer 19

Regulates the extracellular compartment, the interstitial fluid to ensure that the functioning of neurons are not compromised as a result in changes in concentrations of certain substances within the blood.

Question 20

Give some examples of substances that may the BBB regulates against.

Answer 20

Potassium
Circulating neurotransmitters, hormones
Xenobiotics this can include drugs

Question 21

Explain the structure of a general capillary.

Answer 21

Structurally general capillaries facilitate before passive paracellular and transcellular transport. The endothelial cells which line the general capillaries have pores between the cells usually about 4nM which allows substance exchange as well as some possessing fenestrations (holes through the cells themselves) if particularly leaky which can be around 20-100nM width. These also have a high capacity for vesicular transport by containing pinocytic vesicles for example.

Question 22

Explain the structure of a brain capillary.

Answer 22

The endothelial cells which line the brain capillaries contain tight junctions which hold the cells together, meaning there are no pores - preventing substances from moving paracellularly. Pericytes are also present which to help control movement. There are also astrocyte foot processors present which surround the capillary which are involved in the maintenance of tight junctions. There are no intracellular pores, fenestrations and no transporter proteins to help facilitate the movement of substances across the endothelium.

Question 23

Therefore in reference to the structure of the brain capillary how do substances move across the BBB.

Answer 23

They must move transcellularly (across endothelial cells), this can either occur passively (which the majority of substances do if small and uncharged) or by active transporters.

Question 24

Which part of the brain is not covered by the BBB?

Answer 24

Referred to as circumventricular organs, these are parts of the brain that require the movement of substances in and out that wouldn’t usually be able to cross the BBB.
This includes the Posterior pituitary - which secretes protein hormones that need to get into circulation so blood vessels need to be leaky.
And the area postrema (chemoreceptor trigger zone) which triggers vomiting in response to toxic substances- obviously do not want these toxic substances passing into the brain.

Question 25

Which cells separate the circumventricular organs from the rest of the body?

Answer 25

Tanycytes which are specialised cells, forming the tanycytic membrane surrounding the circumventricular organs.