Maintenance of 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 do you get regulation of 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

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

Vasoconstriction
Sympathetic innervation of the main cerebral arteries – causes vasoconstriction when arterial blood pressure is high
Central cortical neurons – neurons within the brain itself can release neurotransmitters such as catecholamines that cause vasoconstriction
Dopaminergic neurons – produce vasoconstriction (important in regulating differential blood flow to areas of the brain that are more active)

Vasodilation
Facial nerve stimulation – can cause a little bit of vasodilation

Question 9

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

Answer 9

They are surrounded by pericytes, 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

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 (Low pH causes vasodilation)
Anoxia 
Adenosine 
K+ 
Other (e.g. kinins, prostaglandins, histamine, endothelins)

Question 14

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

Answer 14

H+ can’t cross the blood-brain barrier but CO2 can
CO2 moves through the blood-brain barrier into the smooth muscle cells.
Within the smooth muscle cells, in the presence of carbonic anhydrase, the CO2 reacts with H2O to form HCO3- and H+
This generated H+ within the smooth muscle cells cause smooth muscle relaxation

Question 15

Describe how nitric oxide (NO) causes vasodilation.

Answer 15

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

Question 16

Where is CSF produced?

Answer 16

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

Question 17

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

Answer 17

Circumventricular organs

Question 18

Describe the passage of CSF through the ventricular system.

Answer 18

CSF is produced by specialized ependymal cells of the choroid plexus
From lateral it goes through the foramen of Monro to the 3rd ventricle
From the 3rd, 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 19

What is the volume of CSF in a normal person?

Answer 19

80-150 mL

Question 20

What is the volume of CSF formed per day?

Answer 20

450 mL/day

Question 21

State three functions of the CSF.

Answer 21

Protection (chemical and physical)
Nutrient provision to neurons
Transport of molecules

Question 22

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

Answer 22

Capillaries in brain have endothelial cells with very tight junctions, gives tight control of what can pass through capillary wall.
Capillaries also surrounded by pericytes with end-feet running along the capillary wall
When the pericytes contract more likely molecules will leave capillary

Question 23

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

Answer 23

Lipophilic (non-polar)

Question 24

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

Answer 24

Water pass through aquaporin molecules

Glucose passes through Glut 1 transporters

Question 25

Name three circumventricular organs.

Answer 25

Sensory
Subfornical organ
Organum vasculosum of the lamina terminalis

Secretory
Median eminence region of the hypothalamus

Question 26

State four molecules with lower concentration in the CSF than the plasma.

Answer 26

K+
Calcium
Amino acids
Bicarbonate

Question 27

State two molecules with higher concentration in the CSF than the plasma.

Answer 27

Mg

Cl

Question 28

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

Answer 28

It isn’t

Question 29

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

Answer 29

CSF slightly more acidic

Question 30

How do Parkinson’s treatments increase dopamine levels when dopamine cannot cross the BBB?

Answer 30

Co-administration of L-DOPA (A precursor to dopamine which can cross BBB) and Carbidopa (which prevents to conversion of L-DOPA to dopamine outside of the brain but also cannot cross BBB)

Question 31

What common treatment had adverse affects on CNS from crossing BBB?

Answer 31

H1 antihistamines caused drowsiness because Histamine in used in brain to regulate wakefulness and the antihistamines could cross BBB - Modern Antihistamines are polar and cannot cross, while old-fashioned ones are sometimes sold as sleeping pills