Case 3 - BBB

Question 1

blood vessels

Answer 1

• Large arteries are 2-5 mm in diameter  carotid vessels that branch of and feed head and neck
• Smallest capillaries are 6-8 micrometres
• So MRI cannot see them
• Both large and small vessels matter in vascular cognitive impairments –> can lead to vascular dementia

Question 2

BBB structure

Answer 2

1. Endothelial cell with tight junctions  look into the junctions (tight junctions, adherens junction, etc.)
2. Pericyte
3. Astrocyte endfeet
   - The pericytes and astrocytes secrete factors that make the endothelial cells produce junction proteins to form the BBB
   - Microglia are in close relation with the capillaries
   - Tight but not completely impermeable
   * High energy demand

Question 3

Transport across BBB

Answer 3

• Passive diffusion:
• Very small molecules (gases)
• Lipophilic molecules
• Low polarity –> high charged
• Active diffusion:
• ABC transporters –> drugs, xenobiotics, Abeta
• Carrier-mediated transport –> specific molecule transporters (like glucose, amino acids, hormones, etc.)
• Receptor-mediated transport -> molecule binds to receptor which is then endocytosed
• Ion transport

Question 4

BBB dynamics

Answer 4

Depends on:
- Diet
- Time of day (circadian rhythm)
- Ageing (and young age)
- Stress
- Toxins
- Microbiome gut

Question 5

neurovascular unit (structure)

Answer 5

• Neurovascular unit –> neurons + associated capillary + BBB
• Endothelial cells
• Pericytes
• Astrocytes
• Microglia
• Neuron
• Oligodendrocytes
• Oligodendrocyte precursor (releases factors that alters NVU)

Question 6

NVU function

Answer 6

• Neuronal activity influences diameter of capillaries and communicates with astrocytes to get more blood flow to get more nutrients
• Neurons –> neurotransmitter –> astrocyte –> hormones –> capillary –> effect (dilation/constriction)

Question 7

microglia

Answer 7

• When the permeability increases microglia can guard the brain
• Remove dying cells, microorganisms, debris, etc.
• Functions:
• Phagocytosis
• Inflammation
• Angiogenesis
• Synaptic remodelling
• When activated they retract their ‘arms’ and expand their soma  produce more ROS to kill, and more cytokines to cause other cells to join and cause inflammation (not a bad thing if appropriate and not chronic)
• Microglia respond to BBB break when they find brain-foreign molecules