Central Blood Flow Regulation and the Blood-Brain Barrier

Question 1

How much oxygen is supplied to the brain per minute?

Answer 1

55 ml/100g of tissue/min

Question 2

Why is there a vast surplus of glucose delivery to the brain?

Answer 2

Because the brain can only metabolise glucose Ketone bodies can be metabolized if there is a shortage of glucose but glucose is the main nutrient

Question 3

Blood glucose below what value will lead to loss of consciousness, coma and death?

Answer 3

2 mM

Question 4

On what levels can you regulate cerebral blood flow?

Answer 4

Mechanisms affecting total cerebral blood flow Mechanisms that relate activity to requirement in specific brain regions by altered localised blood flow

Question 5

Between what range in mean arterial blood pressure can autoregulation maintain a constant cerebral blood flow?

Answer 5

60-160 mm Hg

Question 6

Name one important factor to do with the smooth muscle lining arterioles that allows regulation of blood flow.

Answer 6

Myogenic Mechanism – when the smooth muscle surrounding arterioles is stretched, it will contract to maintain a constant blood flow This occurs when there is a change in blood pressure in the body

•Stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP. This alters radius and hence flow.

Question 7

What are the two types of control of cerebral blood flow regulation?

Answer 7

Neural and Chemical

Question 8

What are the four types of neural control of cerebral blood flow?

Answer 8

Sympathetic innervation of the main cerebral arteries – causes vasoconstriction when arterial blood pressure is high to reduce the blood flow

Parasympathetic (facial nerve) stimulation – can cause a little bit of vasodilation

Central cortical neurons – neurons within the brain itself can release neurotransmitters such as catecholamines (adrenaline/NA) that cause vasoconstriction

Dopaminergic neurons – release dopamine and cause vasoconstriction (important in regulating differential blood flow to areas of the brain that are more active)

Question 9

What feature do capillaries in the brain have that allow them tocontract?

Answer 9

They are surrounded by pericytes, which are contractile cells They are a type of brain macrophage that have several functions e.g. contractile, immune function, transport properties

Question 10

What do the dopaminergic neurons affecting cerebral blood flow innervate?

Answer 10

Pericytes around capillaries and smooth muscle around arterioles.

Pericytes are contractile cells and dopamine can make them contract and hence make the capillaries contract

Dopaminergic neurons use these mechanisms to divert blood flow to areas in brain that are more active

Question 11

Dopaminergic neurons cause contraction of pericytes via which receptors?

Answer 11

Aminergic and serotoninergic neurons

Question 12

Which fibres innervate the main arteries in the brain?

Answer 12

Sympathetic fibres

Question 13

Name some chemical factors that increase blood flow to particular tissues.

Answer 13

Carbon dioxide

NO

pH

Anoxia

Adenosine

K+

Other (e.g. kinins, prostaglandins, histamine, endothelins)

these factors are generally localised and they are all vasodilators

Question 14

How does change in pH affect blood flow?

Answer 14

The lower the pH (the higher the H+ concentration) the more the vesselvasodilates

Question 15

Describe how carbon dioxide indirectly causes vasodilation in the cerebral vessels.

Answer 15

H+ ions can’t cross the blood-brain barrier but carbon dioxide can Carbon dioxide moves from the blood through the blood-brain barrier into the smooth muscle cells Within the smooth muscle cells, in the presence of carbonic anhydrase, the carbon dioxide reacts with water to form bicarbonate and H+ ions This internally generated H+ ions within the smooth muscle cells cause smooth muscle relaxation (vasodilation)

Question 16

Describe how nitric oxide (NO) causes vasodilation.

Answer 16

Nitric oxide stimulates guanylyl cyclase Guanylyl cyclase converts GTP - cGMP cGMP causes vasodilation

Question 17

Where is CSF produced?

Answer 17

Choroid plexus – these are a specific plexus cells associated with the ventricles (in particular the lateral ventricles)

Question 18

What name is given to parts of the brain that receive blood flowlike anywhere else but do not have a blood-brain barrier?

Answer 18

Circumventricular organs - contain fenesterated capillaries. They generally need this due to their function of secreting into the plasma OR sampling the plasma

Examples include subfonical organ, OVLT (Y1 enteroendocrine)

Question 19

Describe the passage of CSF through the ventricular system.

Answer 19

CSF is produced by specialized ependymal cells of the choroid plexus (mainly in the lateral ventricles) From the lateral ventricles it goes through the foramen of Monro to the 3rd ventricle From the 3rd ventricles, CSF flows down the cerebral aqueduct to the 4th ventricle From the 4th ventricle it enters the subarachnoid space (via medial and lateral apertures) and eventually drains back into the venous system via arachnoid granulation

Question 20

What is the volume of CSF in a normal person?

Answer 20

80-150 mL

Question 21

What is the volume of CSF formed per day?

Answer 21

450 mL/day

Question 22

State three functions of the CSF.

Answer 22

Protection (chemical and physical)

Nutrient provision to neurons

Transport of molecules

Question 23

Describe the structure of the blood-brain barrier. Which cells are involved?

Answer 23

The capillaries in the brain have endothelial cells with very tight junctions so there is tight control of what can pass through the wall of the capillary

pericytes also help to maintaining capillary integrity and function. Peripheral capillaries have hardly any pericytes but BBB capillaries have a lot of pericytes

The capillaries are also surrounded by end-feet from astrocytes running along the capillary wall (see slide 32)

When the pericytes contract they make it more likely for the molecules to leave the capillary

Question 24

What type of molecule can cross the blood-brain barrier easily?

Answer 24

Lipophilic molecules

Question 25

How do water and glucose cross the blood-brain barrier?

Answer 25

Water pass through aquaporin molecules Glucose passes through Glut 1 transporters

Question 26

Name three circumventricular organs.

Answer 26

Median eminence region of the hypothalamus

Subfornical organ

Organum vasculosum of the lamina terminalis (OVLT)

Neurohypophysis

Question 27

State four components that have a lower concentration in the CSF than the plasma.

Answer 27

K+ Calcium Amino acids Bicarbonate

Question 28

State two components that have a higher concentration in the CSF than the plasma.

Answer 28

Magnesium Chloride

Question 29

How is the osmolarity different between the CSF and the plasma?

Answer 29

The same

Question 30

How is the pH different in the CSF compared to the plasma?

Answer 30

CSF is slightly more acidic