Blood brain barrier and drug delvery

What is the primary function of the BBB?

• Maintains CNS homeostasis by controlling what enters/leaves the brain

• Prevents inflammation and neurotoxicity from blood-borne toxins/pathogens

• Protects neuronal signalling stability

Name 3 components of the BBB

1. Special brain capillaries with tight junctions

2. CSF drainage system

3. Active Efflux Transport (AET) pumps

How do brain capillaries differ from systemic capillaries?

• Tight junctions reduce pores to <10Å (vs. 20–100Å in systemic capillaries)

• Covered by astrocyte foot processes

• Nearly impermeable to paracellular transport

What 3 cell types interact at the BBB?

1. Endothelial cells (capillary wall)

2. Astrocytes (glial cells)

3. Pericytes (support cells)

What properties allow drugs to cross BBB passively?

• MW <500 Da

• Lipophilic (non-polar)

• Unionized state

How does CSF contribute to BBB function?

• Bathes brain surfaces but has limited drug exchange

• Drains to venous sinuses, removing drugs

How does stroke affect BBB?

• Disrupts tight junctions → hyperpermeability

• Increases paracellular leakage

How should hydrophilic drug dosing change in stroke?

Reduce doses (enhanced uptake risks toxicity)

What happens if BBB fails?

Uncontrolled inflammation, toxicity, and impaired neuronal homeostasis

How do astrocytes contribute to BBB?

• Provide physical support (foot processes)

• Host efflux pumps/enzymes that degrade drugs