Clinical significance of the BBB (7.2)

Question 1

Describe the structure and function of the BBB

Answer 1

Function: Maintains homeostasis; prevents damaging/toxic substances from entering the brain; protects the brain (e.g. electrolyte fluctuations); provides essential nutrients for the brain

Structure: Formed from continous non-fenestrated endothelial cells with tight junctions, surrounded by a basement membrane. Astrocyte foot processes contact the endothelium. Pericytes are associated with the endothelium, maintaining the health and function of the cells.

Question 2

Outline the factors which determine whether a substance is able to cross the BBB

Answer 2

The following characteristics favour transport of substances:

• Low molecular weight
• No ionic charge
• Lipophilic

Transport is also dependent upon whether the molecule has an:

• Associated plasma protein
• Associated active transport system
  
  • Glucose transporter
  • System L - Transports large neutral amino acids e.g. Phe
  • Monocarboxylic acid transporters
• Undergoes efflux
  
  • P-glycoprotein
  • MDRP
• Undergoes metabolism at the BBB

Question 3

Give examples of physiological implications of the BBB

Exploited/problematic

Answer 3

Question 4

Give examples of how the BBB can be overcome to allow for the delivery of drugs

Answer 4

• Use of pro-drugs
  
  • Example: L-DOPE
• Use of high systemic doses
• Invasive drug delivery
  
  • Intracavity implants; intrathecal

Question 5

Give examples of potential future mechanisms for drug delivery across the BBB

Answer 5

• Incorporation of drugs into biodegradable polymers
• Design of specific efflux pump inhibitors OR design drugs with reduced affinity for efflux pumps
• Design drugs which mimic the structure of molecules which are able to cross the BBB
• Use of exosomes

Question 6

Outline the relationship between the BBB and disease

Answer 6

Question 7

State the mechanisms by which selectivity of the BBB is acheived

Answer 7

Transporters

Immunological

Metabolic - BBB enzymes digest molecules

Physical - Tight junctions between endothelial cells

Question 8

State the regions of the brain which are devoid of a BBB and the possible reason for this

Answer 8

• CTZ (chemoreceptor trigger zone) - Allows the detection of toxin present in the blood
• Pineal gland - Allows for secretion of melatonin
• Posterior pituitary gland - Allows for the passage of hormones