Blood Brain Barrier

Question 1

What are the proteins that make up tight junctions?

Answer 1

Claudin, JAM (junctional adhesion molecule), Occludin

Question 2

What does a molecule pass through to get from the capillary lumen to the brain capillary lumen?

Answer 2

Crosses the luminal and ablumincal layer of the endothelial cells through a transport protein, interacts with modification enzymes.

Question 3

What transports most physiological substances across the membrane?

Answer 3

Monocarboxylate Transporter -1 (MCT1) moves: Lactate, pyruvate, acetate, butyrate Exercise, hypoglycemia Ketones (D--hydroxybutyrate, acetoacetate) Fasting, ketogenic diet Glucose - GLUT1 Amino acids - LAT1

Question 4

How is MCT1 expression regulated?

Answer 4

MCT1 is expressed more in individuals that have a high ketone body diet. Brain cells are able to adapt and increase transporters.

Question 5

What are the common efflux proteins?

Answer 5

P-glycoprotein, MRP1,2,3

Question 6

What are some BBB diseases?

Answer 6

Multiple sclerosis Alzheimer’s Disease Epilepsy Glucose transporter dysfunction (De Vivo disease) Creatine transporter defect Meningitis

Question 7

What is the function of the LRP protein?

Answer 7

Binds to molecules and moves them across the cell.

Question 8

What is diapedesis?

Answer 8

Immune cells are able to progress into the brain by attaching and crossing through the cells. This is chemokine directed.

Question 9

When is the BBB/NVU established?

Answer 9

The early embryo consists of the vascular endothelium, neuroepithelium, and neural tube cavity, vasculature grows toward Wnt through the neuroepithelium – the BBB is there from the beginning but does change over time.

Question 10

How does the BBB differ from the CSF-brain barrier?

Answer 10

The endothelial cells (Endo) have luminal tight junctions forming the physical barrier. Outside the endothelial cell is a basement membrane (bm) which also surrounds the pericytes (Peri). Around all these structures are the astrocytic endfeet processes from nearby astrocytes (As endfoot). All these structures together are often referred to as the neurovascular unit. The blood–CSF barrier, choroid plexus blood vessels are fenestrated and form a nonrestrictive barrier; however, the epithelial cells have apical tight junctions that restrict intercellular passage of molecules.

Question 11

What transporters are responsible for forming the CSF?

Answer 11

To reduce CSF production:
Acetazolamide – inhibits CA
Ouabain - Na/K ATPase inhibitor
Furosemide – Na/K/Cl transporter