Blood Brain Barrier

Question 1

How long after total cerebral blood flow interruption does it take to become unconscious, and how long until brain damage?

Answer 1

Four seconds - Unconscious

Few minutes - Irreversible damage

Question 2

What does the brain use for energy?

Answer 2

Only glucose - cannot metabolise anything else

Will utilise metabolised ketones if there is a glucose shortage

Question 3

What is the minimum Blood-Glucose concentration?

Answer 3

2 nM

If lower, unconsciousness, coma and death may result

Question 4

How is Cerebral Blood Flow autoregulated?

Answer 4

Myogenic response:

• Smooth muscle lining arteries stretches in response to blood flow
• Increase in wall pressure leads to contraction of smooth muscle that decreases cerebral blood flow
• Occurs when there is a change in BP in the body

Also Local delivery is regulated by relative needs of brain tissue by local autoregulation

Question 5

What are the four methods of Neural Control of Cerebral blood flow?

Answer 5

Sympathetic nerve stimulation

Parasympathetic (Facial) Nerve Stimulation

Central Cortical Neurones

Dopaminergic Neurones

Question 6

How do Sympathetic nerves control Cerebral Blood Flow?

Answer 6

Sympathetic innervation of the main cerebral arteries can cause vasoconstriction when the arterial BP is high

Question 7

How do Parasympathetic nerves regulate Cerebral Blood Flow?

Answer 7

Facial nerve fibres cause a slight vasodilation

Question 8

How do Central Cortical Neurones regulate Cerebral Blood Flow?

Answer 8

Neurones within the brain can release neurotransmitters such as catecholamines that cause vasoconstriction

Question 9

What are Pericytes?

Answer 9

Type of Brain Macrophage that surround capillaries

They are contractile, and also provide immune function and have transport properties

Question 10

How do Dopaminergic Neurones regulate cerebral blood flow?

Answer 10

Produce Vasoconstriction

They innervate smooth muscle surrounding arterioles and the pericytes around capillaries

Cause contraction of pericytes to decrease blood flow toa particular area, diverting blood to other, more active areas

Question 11

Describe the pattern of Vascularisation in CNS tissues:

Answer 11

Arteries enter the CNS tissue from as branches of the surface pial vessels. These branches penetrate into the brain parenchyma branching to form capillaries which drain into venules and veins which drain into surface pial veins.

Question 12

What are the three main Chemical methods of control of Cerebral Blood flow?

Answer 12

pH

K+

CO₂

Nitric Oxide

Question 13

How does pH control Cerebral blood flow?

Answer 13

Active cells produce lactic acid

H+ ions cause a drop in pH which causes vasodilation in that area

• a local regulation

Question 14

How do Potassium ions control Cerebral blood flow?

Answer 14

K+ is released at a stage of the action potential and acts as a Vasodilator

Question 15

How does CO₂ regulate cerebral blood flow?

Answer 15

Indirectly - H+ ions cannot cross the BBB, CO₂ can

Carbonic anhydrase in the brain leads to production of H+ which acts as a Vasodilator

Question 16

How is CSF produced?

Answer 16

By the Choroid plexus associated with the lateral ventricles - has Capillaries surrounded by Ependymal cells

Ependymal cells secrete molecules into the ventricles to make CSF

These cells have tight junctions, so the composition of CSF is different to blood

Question 17

What is the Path of CSF?

Answer 17

Lateral ventricles

3rd Ventricle (via interventricular foramina)

Cerebral aqueduct

4th Ventricle

Subarachnoid space (via medial and lateral apertures)

Question 18

What is the normal volume of CSF?

How much is made per day?

Answer 18

80-150ml

450 ml/day

Question 19

What is the function of CSF?

Answer 19

Protection (Chemical & Physical)

Nutrition of Neurones

Transport of molecules

Question 20

What are the functions of the BBB?

Answer 20

Protects the brain tissue from certain toxins and circulating transmitters like catecholamines

Protects brain from wide variations in ion concentrations

Question 21

How are the capillaries of the brain different to the rest of the body?

Answer 21

They have very tight junctions - non-fenestrated

Question 22

What two things make the blood-brain barrier?

Answer 22

The Tight Junctions (Main)

Pericytes with end-feet that run along the capillary wall (molecules more likely to escape when they contract)

Question 23

What are three ways molecules may cross the BBB?

Answer 23

By being lipophilic - e.g. alcohol and anaesthetics

Via transport mechanisms

Via Circumberntricular organs

Question 24

Name 4 transport mechanisms that allow specific transport of molecules through the BBB:

Answer 24

Water via Aquaporins

Glucose via GLUT1

Amino acids via 3 different transporters

Electrolytes via specific transporter systems

Question 25

What are circumventricular organs? Name three:

Answer 25

Structures with fenestrated capillaries They therefore lie outside the BBB Molecules can readily pass from blood to CSF/ECF - Median eminence region of the hypothalamus - Subfornical organ (SFO) - Organum vasculosum of the lamina terminalis (OVLT)

Question 26

What are the main differences in the composition of Plasma and CSF?

Answer 26

Same Osmolarity, CSF slightly more Acidic ## Footnote * *CSF has lower:** - K+ - Ca2+ - Amino Acids - Bicarb * *CSF has higher:** - Magnesium - Chloride