lecture 4 Blood Brain Barrier Flashcards
Blood–CSF barriers
Choroid plexus epithelial cells
Arachnoid membrane
Choroid plexus is
main site of entry for Ca2+ into the brain.
What is the blood-brain barrier
A highly selective semi-permeablebarrier separating the circulating blood from the brain and spinal cord
types of cells that make up BBB
Brain endothelial cells, basement membrane, pericytes, astrocytes, neurons
_________ cells that precludes entrance of
substances into the brain
tight-junctioned brain capillary
endothelial
BBB has gaps where
in some sensory (area postrema) and secretory area
______ are responsible for the formation and the maintenance of the BBB
Astrocytes
what are the main Cellular constituents of the BBB (%)
Brain endothelial cells Basement membrane Pericytes Astrocytes Neurons
fenestrations occur in
periphery (a gap)
TJs are one mode of cell-cell adhesion, sealing the ________ between endothelial cells.
aqueous paracellular diffusional pathway
Linked together by a complex of proteins which span the inter-endothelial space creating
Tight Junctions
Individual TJ strands then ____ and tightly associate with strands in the apposing membrane of _____to form paired strands, intercellular distance becomes nonexistent….. “kissing points
laterally,,adjacent cells
what are the 4 main the interaction between integral membrane proteins
Junctional Adhesion Molecules
Occludin
Claudin
Adherence Junctions
Junctional Adhesion Molecules with a single transmembrane domain, was shown to associate laterally with TJ strands, but
not to constitute the strands per se
Zonulae Occludins are ____conditions where BBB breakdowns and TJ can formed wit/without
decreased without
Adherens Junctions______ found in many tissues
Adhesive cell-cell contact
3 main functions of BBB important
Physical:BECs & tight junctions
Transport: Specialized transporters
Metabolic: enzymes
Cadherin dimers form
cell-cell adhesion
____is critical for the normal functioning of cadherins, which have a _____ binding site in their extracellular domain
calcium
_____ is a major constituent of TJ strands
Claudin
Experiment: WT and Cldn 5-/- embryos injected with a
low molecular mass tracer Findings and authotrs hypothesis
WT mice had no tracer from CNS, whereas
Cldn 5-/- mice showed had tracer throughout CNS parenchyma
Authors hypothesis: BBB is loosened in a size-selective manner in Cldn 5-/- mice.
Main molecular traffic routes across the BBB
1) Transcellular Diffusion
2) Transport Proteins
Solute Carriers
ABC Efflux Transporters
3) Trancytosis
Receptor-mediated
Adsorptive
Transcellular diffusion is dependent upon
lipid solubility-High oil/water partitioning coefficient (K)