BBB Structure and role structure plays in function

• Components :

  • endothelial cells

  • tight junctions

  • astrocytes

    • associate with endothelial cells and one another through gap junction (GJ) bridges made up of connexin hexamers.

  • pericytes

    • role in endothelial proliferation and angiogenesis

    • after injury , tumors , low 02 events , the brain is constrained by skull

    • cancer and other diseases down regulate pericytes , causing :

      • abnormal vasuulogenesis

      • endothelial hhyberplasia

      • increased permeability to BBB

• what can enter ?

  • small

  • lipid soluble , non-polar

  • low charge

• barrier functions :

  • Paracellular barrier = restricts the free movement of H2O soluble compounds

  • Transcellular barrier = inhibits transport of substances to the cytoplasm

  • Enzymatic barrier = enzymatic degradation of compounds

  • Cerebral Endothelium = Express a large number of efflux transporters

    • some drugs might enter , but are exported very quickly

• functions :

  • separates components of the circulating blood from neurons

    • maintains the chemical composition of the neuronal microenvironment

  • It protects the brain from pathogens and endows relative immune privilege

  • restricts transport of cells or toxins into the CNS

  • regulates the transport of nutrients and metabolites in and out of the brain

Transport mechanisms

• paracellular pathway doesn't really exist , because tight junctions block it

• only small , water-soluble molecules can diffuse through the BBB

Impact of BBB disruption

• diseases , inflammatory

• start to get interleukin accumulation

• stroke ➡️ low O2 ➡️ low ATP ➡️ breakdown of BBB

  • ATP and calcium are needed for proper maintenance of BBB

Appreciation of drug delivery obstacles

• how can we ?

• lipid soluble or transport mechanisms