Central Blood Flow Regulation and the Blood-Brain Barrier

Question 1

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

Answer 1

2 mM

Question 2

On what levels can you regulate cerebral blood flow?

Answer 2

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

Question 3

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

Answer 3

60-160 mm Hg

Question 4

How is TOTAL cerebral supply blood supply regulated

Answer 4

Autoregulation. This involves the myogenic mechanism (VSMC)- stretch-sensitive cerebral vascular smooth muscle contracts at high BP and relaxes at lower BP. This alters radius and hence flow.

Question 5

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

Answer 5

Neural and Chemical

Question 6

What are the four factors that affect neural control of cerebral blood flow?

Answer 6

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 7

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

Answer 7

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 8

What do the dopaminergic neurons affecting cerebral blood flow innervate?

What is the purpose of the dopamingergic neurones doing this?

Answer 8

Pericytes around capillaries and penetrating 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 9

Dopaminergic neurons cause contraction of pericytes via which receptors?

Answer 9

Aminergic and serotoninergic neurons

Question 10

Which fibres innervate the main arteries in the brain?

Answer 10

Sympathetic fibres

Question 11

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

Answer 11

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 12

How does change in pH affect blood flow?

Answer 12

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

Question 13

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

Answer 13

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 14

Describe how nitric oxide (NO) causes vasodilation.

Answer 14

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

Question 15

Where is CSF produced?

Answer 15

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

Question 16

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

Answer 16

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 17

Describe the passage of CSF through the ventricular system.

Answer 17

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 18

What is the volume of CSF in a normal person?

Answer 18

80-150 mL

Question 19

State three functions of the CSF.

Answer 19

Protection (chemical and physical)

Nutrient provision to neurons

Transport of molecules

Question 20

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

Answer 20

Lipophilic molecules

Question 21

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

Answer 21

Water pass through aquaporin molecules Glucose passes through Glut 1 transporters

Question 22

Name three circumventricular organs.

Answer 22

Median eminence region of the hypothalamus

Subfornical organ

Organum vasculosum of the lamina terminalis (OVLT)

Neurohypophysis

Question 23

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

Answer 23

K+ Calcium Amino acids Bicarbonate

Question 24

What may protein in the CSF indicate

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

Answer 24

May indicate breach/damage

Magnesium and Chloride ions

Question 25

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

Answer 25

The same

Question 26

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

Answer 26

CSF is slightly more acidic

Question 27

How do Vessel BBB properties differ in deeper vessels.

Answer 27

Vessel BBB properties increased in deeper vessels.

Question 28

bbb at level of?

Answer 28

CNS capillaries

Question 29

CVO- Circumventricular organs - ventricular ependymal lining

Answer 29

•The ventricular ependymal lining close to these areas can be much tighter than in other areas, limiting the exchange between them and the CSF.

Question 30

Why do Circumventricular organs need access to the blood

Answer 30

• the posterior pituitary and median eminence secrete hormones
• the area postrema samples the plasma for toxins and will induce vomiting
• others are involved in sensing electrolytes and regulate water intake.

Question 31

BBB- capillaires of CNS parenchyma are dervied from

Answer 31

surface pial vessesl

Question 32

BBB capillaries have tight junctions

Answer 32

at endothelial cell-cell contacts

Question 33

2 differences between peripheral and BBB capillaries

Answer 33

Blood brain barrier:

High dense pericyte coverage

Covered in end feet from astrocytes

Question 34

Treatment for parkinons: Dopamine can’t get past BBB so use what?

What is the issue with this

Solution

Answer 34

L-DOPA

Converted peripherally into dopamine

Coupled with Carbidopa- DOPA decarboxylase inhibitor

• the inhibitor can’t cross the blood brain barrier so doesn’t affect the dopamine production.