Pharmacology of the Blood-Brain Barrier

Blood-Brain Barrier (BBB)

• The BBB is a selective barrier between blood and CNS compartments that:
  • Prevents pathogens, small hydrophilic molecules, proteins, and leukocytes from entering the CNS
  • Allows nutrient and oxygen supply to neurons
  • Regulates blood pressure
  • Forms an interface for immune- and nervous system crosstalk

Structure of the Blood-Brain Barrier (BBB)

• The BBB consists of different barriers, including circumventricular organs and brain vasculature
• Brain vasculature has:
  • 600 km of vessels in the human brain
  • Each neuron has its own capillary
  • The largest barrier interface in the brain
• Vessel composition differs between arterioles, capillaries, and venules
• Cerebral capillaries:
  • Are not fenestrated like peripheral capillaries
  • Have a lower transcytotic rate than peripheral endothelial cells
  • Have different barrier properties (~1500-2000 Ω/cm2 vs. ~30 Ω/cm2 in peripheral capillaries)
  • Have an increased number of mitochondria
  • Are covered with astrocytic endfeet
  • Have the highest coverage of pericytes compared to peripheral vessels

Neurovascular Unit

• The neurovascular unit consists of:
  • Endothelial cells
  • Pericytes/smooth muscle cells
  • Astrocytes
  • Neurons
• Extended parts of the neurovascular unit include:
  • Microglia
  • Blood cells

Pericytes

• Pericytes:
  • Surround the endothelial cell layer
  • Are embedded between the endothelial and parenchymal basement membrane
  • Are important for the function and development of the BBB
  • Influence several mechanisms in the brain (immune cell infiltration, blood flow regulation)
  • Are a heterogeneous cell type dependent on vessel type

Astrocytes

• Astrocytes:
  • Have direct contact with vessels, neurons, synapses, and other glial cells
  • Influence tightness and transport mechanisms across the BBB
  • Are essential for water and ion homeostasis in the brain (special water and ion channels at their endfeet)
  • Are highly reactive after disturbance

This quiz covers the basics of the blood-brain barrier, its structure, disease implications, and strategies to overcome the barrier. It also explores the BBB as a target for specific diseases, including COVID-19.