Blood Brain Barrier Flashcards
(23 cards)
Who, when and how the impermeability of the BBB was first established?
- Edwin Goldman
- 1913
- Injected dye in rats outside of the brain + injected dye in rats in the brain
- Dye never crossed into or out of brain – conclusion … bbb
Illustrate the molecular structure of the tight junction in the brain endothelial cells (+ 3 proteins)
IN NOTES
Identify 3 specific proteins associated with the BBB
- Claudin
- Occludin
- Adherin junctions
List and explain the principle of FOUR drug-delivery strategies that scientists have explored to improve drug delivery across the BBB
- Absorption occurs between (-) charges
- can alter albumin or therapeutic drugs to have more (+) charges - Membrane receptors
- can be fooled with ligands that are complexed with drugs
- endocytosis can occur - Active efflux
- this can be inhibited to enhance intracellular retention of drugs - Passive diffusion
- improved by increased lipophilicity (hydro)
Explain the mechanism by which EDTA could increase the permeability of the BBB to drugs
EDTA coordination complex can bind with Ca2+ (acts as s calcium chelator) – this loosens the tight junctions and allows paracellular diff
- removes Ca2+ and destabilizes ionic reaction
Blood-Brain Barrier
- Extremely selective filter that coats the blood vessels in the brain, preventing harmful substances in the bloodstream from passing through
- Found between blood and the CNS
- Two component system ( blood-CSF barrier and blood-brain barrier) –> diffusion of drugs are prevented by both BBB and BCB
- BBB formed by endothelial cells
- signals come from neurons and cells
Vascular endothelial cells
Lines blood vessels
Tight junctions
- Tight junctions impede the passage of macromolecules
- seal adjacent epithelial cells in a narrow band just beneath their apical surface
Neurovascular unit
- BBB components and neurons that are essential for the health and function of the CNS
Paracellular diffusion
- transfer of substances across an epithelium by passing through the intercellular space between the cells (no tight junctions)
Amyloid beta + Alzheimers
- Amino acids that are involved in Alzheimer’s disease
- The main component of the amyloid plaques found in the brains of Alzheimer patients
- In Alzheimers, plaque buildup is due to disfunctional BBB (initially caused by several factors which causes AB secretion and in turn influx into brain)
- diabetes can also lead to Alzheimers
Absorptive mediated transcytosis
- binding of substances to the negative charges on the BBB PM
- This is where endocytosis occurs
Membrane receptor
Proteins that are located on the plasma membrane and can transmit a signal when a ligand is bound it it.
Celebrospinal fluid (CSF)
- acts like a cushion/buffer for brain’s cortex
- provides basic mechanical and immunological protection to the brain
Two features of brain endothelial cells
- LOTS of Tight junctions
2. Lil amt of caveolae
Caveolae
- membrane bound vesicles involved with endocytosis and transcytosis
- 14 fold less caveolae than in non neural
Gate barrier function of tight junctions
- junctions are made of continuous strands that extend circumferentially around the endothelial
- prevents movement of molecules to go in between cells (paracellular)
Fence barrier function of tight junctions
- restrict the movement of membrane molecules between the functionally distinct apical and basal sides
Tight junction- claudin and occuldin characteristics
- loops + overhangs
- overhangs interact with linker proteins attached by cytoskeleton
- can essentially be loosened
Adherins junctions
- stabilize cell adhesion and limit any paracellular diffusion
- located below tight junctions
- ionic interaction between cadherins (meant to stabilize cell interaction) which makes it possible to interfere with
Brain injury
BBB breakdown –> no tight junctions –> angiogenesis + restoration
- trauma related to BBB disfunction
- entry of K+ or albumin into BBB results in seizures
Occudin
- contributes to fence and gate
- key anchorage site for actin cytoskeleton
- determines cell fate and development
Claudins
- determine the tissue, charge and size selectivity of the paracellular seals
- most important in preventing anions and cations from diffusing through
