BBB and cerebral blood flow regulation

Question 1

give approximate blood supply to brain

Answer 1

55ml/100g tissue/min.

Question 2

What happens when blood flow to brain is reduced by more than 50%

Answer 2

insufficient oxygen delivery function becomes significantly impaired.

Question 3

What period of interrupted CBF will result in unconsciousness?

Answer 3

4 seconds

Question 4

What period of interrupted CBF will result in irreversible damage?

Answer 4

a few minutes.

Question 5

What is syncope?

Answer 5

fainting - temporary CBF interruption.

Question 6

Give some potential causes of syncope.

Answer 6

low BP, postural changes, vast-vagal attack, sudden pain, emotional shock.

Question 7

Explain necessity of large glucose supply to brain.

Answer 7

Brain uses 50-60% body’s glucose. Brain cannot store/synthesise any other energy sauce (ketones in starvation)

Question 8

Give three signs of reduced glucose supply to the brain.

Answer 8

Disorientation, slurred speech, impaired motor function.

Question 9

What happens at glucose concentration levels fall below 2mM (normal fasting = 4-6)

Answer 9

unconsciousness, coma, death.

Question 10

Why must CBF be maintained, efficient, and consistent?

Answer 10

because of the constant need of brain for oxygen and glucose.

Question 11

What 2 types of mechanism regulate CBF

Answer 11

Mechanisms affecting total CBF mechanisms which relate activity to the requirement in specific brain regions by altered localised blood flow.

Question 12

What is the range of auto regulation of total CBF?

Answer 12

60-160mm Hg

Question 13

How is CBF auto regulated?

Answer 13

arteries/arterioles dilate/contract to change blood flow. Stretch sensitive cerebral vascular smooth muscle contracts at High BP and relaxes at lower BP.

Question 14

What happens outside the auto regulatory range?

Answer 14

Below - insufficient supply –> compromised brain function Above - increased flow –> swelling of brain tissue –> increased intracranial pressure = dangerous.

Question 15

Why is local auto regulation needed?

Answer 15

The local brain activity determines the local O2 and glucose demands, therefore local changes in blood supply

Question 16

What two ways is CBF locally auto regulated?

Answer 16

-neural control -chemical control

Question 17

Explain pattern of vascularisation in CNS

Answer 17

arteries enter CNS from branches of surface Pia vessels. Branches penetrate into parenchyma and branch into capillaries.

Question 18

What’s the furthest a neurone might be from a capillary?

Answer 18

100micrometers.

Question 19

What 4 ways do neural factors regulate CBF?

Answer 19

1. sympathetic nerve stimulation to main cerebral arteries –> vasoconstriction. 2. parasympathetic (facial nerve) stimulation –> slight vasodilation. 3. central cortical neurones release vasoconstrictor neurotransmitters e.g. catecholamines (e.g. NA, adrenaline) 4. dopaminergic neurones produce vasoconstriction (localised)

Question 20

What is the function of dopaminergic neurones (locally)?

Answer 20

1. innervate penetrating arterioles and pericytes around capillaries.
2. participate in diversion of CBF –> areas of high activity.
3. dopamine can cause contraction of perictyes via amoinergic + serotoninergic receptors

Question 21

What chemical factors regulate CBF?

Answer 21

CO2 - vasodilator

lower pH - vasodilator

NO - vasodilator

K+ - vasodilator

adenosine - vasodilator

anoxia - vasodilator

other, e.g. kinins, histamines, endothelins, prostaglandins.

Answer 22

What is the effect of pCO2 on CBF (diagram)?

Question 23

How does CO2 cause vasodilation.

Answer 23

CO2 –> carbonic acid –> increased H+ (carbonic anhydrase) –> relaxation –> increased blood flow.

(H+ cannot cross BBB)

Question 24

How can brain activity be mapped?

Answer 24

Imaging - look for increased blood flow.

Increased blood flow equates to increased neuronal activity in CNS.

Question 25

what is the function of the choroid plexus?

Answer 25

produce CSF.

Question 26

How does CSF act as a protective mechanism?

Answer 26

Provides insulation - brain effectively floating in CSF.

Question 27

What lines ventricles, aqueducts and canals of brain?

Answer 27

ependymal cells. Can form choroid plexus in ventricles.

Question 28

Label diagram of ventricles.

Answer 28

Question 29

What is the function of the CSF?

Answer 29

physical and chemical protection. Neurone nutrition. Molecule transport.

Question 30

What is the volume of CSF?

Answer 30

80-150ml

Question 31

How is CSF formed?

Answer 31

Capillaries leaky, but local ependymal cells have extensive tight junctions. Secrete CSF into ventricles (lateral ventricles, 3rd ventricle via interventricular foramina, down cerebral aqueduct into 4th ventricle and into subarachnoid space via medial and lateral apertures) – circulates.

Question 32

Label diagram outlining CSF formation.

Answer 32

Question 33

Diagram showing relative CSF vs plasma concentrations.

Answer 33

Question 34

What is the level of the BBB (at which size of blood vessel is BBB formed)?

Answer 34

CNS capillaries.

Question 35

What are capillaries of CNS derived from?

Answer 35

surface pia vessels

Question 36

Give some features of BBB capillaries?

Answer 36

tight junctions - minimise solute and fluid leakage. Dense pericyte coverage (maintain capillary function) End feet from astrocytes (maintain BBB properties) Influx and efflux transporters control solute flow lipophilic molecules can cross.

Question 37

Give transport systems for water, glucose, aa and electrolytes across BBB.

Answer 37

1. water - aquaporin (AAQP1, AQP4) 2. glucose - GLUT1 3. aa, 3 different transporters. 4. electrolytes, via specific systems.

Question 38

what are circumventricular organs (CVOs)

Answer 38

Area where capillaries lack BBB properties.

Question 39

Give some properties of CVOs.

Answer 39

fenestrated (so leaky). tight ependymal lining to control and limit exchange.

Question 40

Why do CVOs exist?

Answer 40

for secretion of substances into plasma, e.g. **posterior pituitary**, **media eminence** for sampling of plasma. e.g. **area postrema** (vomiting)

Question 41

What can cause breakdown of BBB function?

Answer 41

trauma, inflammation, infection, stroke.

Question 42

Why does the BBB present an issue for pharmacology?

Answer 42

Do you want your drug to access the brain? Many drugs cannot access the brain Many drugs access it too readily.

Question 43

Why do old fashioned antihistamines make people drowsy?

Answer 43

histamine is important for wakefulness. Old fashioned antihistamiens are lipophilic and can cross BBB. Newer antihistamines are polar

Question 44

Why does the BBB affect Parkinsons treatment?

Answer 44

Dopamine cannot cross BBB, precusor L-DOPA can.