Blood Brain Barrier (Almost finished)

Question 1

describe a tight junction and its components?

Answer 1

components: Claudin, JAM, and occludin

Question 2

list key features of the blood-brain barrier (BBB)

Answer 2

Endothelial cell membranes are asymmetrical.
- Luminal vs. abluminal
Substrates entering brain must cross two membranes (and the cytoplasm).
Substances passing through the cytoplasm may be altered by enzymes. (enzymatic barrier)

CSF Secretion
	Na+, Cl-, HCO3- net transport
	H2O by osmosis
	0.2 ml CSF/min.g
Transporters/exchangers/pumps for Na+, K+, H+, anions (Cl-, HCO3-)
Asymmetric distribution

Question 3

compare the BBB to the NVU (neurovascular unit)

Answer 3

a

Question 4

identify basic transporters for nutrient influx

Answer 4

Monocarboxylate Transporter-1 (MCT1) transports lactic acid
GLUT1 moves glucose
LAT1 moves AAs
also: ENT1, CNT2, FATP1, CT1

Question 5

identify major transporters for efflux of drugs

Answer 5

P-glycoprotein is one of several efflux transporters.

Question 6

know when and how the BBB/NVU is formed

Answer 6

At the very beginning when the first vessels appear. Mouse: embryonic brain day 12.5/21; Human: first few weeks fertilization

Question 7

know the link between brain blood flow and the NVU

Answer 7

a

Question 8

list diseases that are linked to dysfunction of the NVU

Answer 8

Working Hypothesis:
When the endothelial cell is dysfunctional, then the cells around it are dysfunctional resulting in a neurological disease.

Multiple sclerosis
Alzheimer's Disease
Epilepsy
Glucose transporter dysfunction (De Vivo disease)
Creatine transporter defect
Meningitis
Pathogenic infections
Bacterial (E. Coli, Citrobacter)
Parasitic (tryp, Lyme, Plasmodium sp.)
Viral infections
HIV, others
Late-stage neurological trypanosomiasis (Sleeping sickness)
Progressive multifocal leukoencephalopathy (PML)
Rabies

Question 9

describe the Trojan Horse model for drug delivery to the CNS

Answer 9

a

Question 10

know how cells of the immune system traffic into the brain

Answer 10

Diapedesis, they either roll in with weak adhesion or use strong adhesion to accomplish emigration

Question 11

What Cells are involved in making CSF?

Answer 11

endothelial cells of the choroid plexus

Question 12

What transporters are essential for CSF formation?

Answer 12

a

Question 13

How can CSF formation be affected by transport inhibitors?

Answer 13

To reduce CSF production:
acetazolamide
ouabain
furosemide

Question 14

What is P-glycoprotein

Answer 14

P-glycoprotein is one of several efflux transporters. they pump therapeutic drugs out of the brain and prevent them from reaching their target!!

Question 15

Glymphatics

Answer 15

In this brain-wide pathway, CSF enters the brain along para-arterial routes, whereas ISF is cleared from the brain along paravenous routes. Convective bulk ISF flow between these influx and clearance routes is facilitated by AQP4-dependent astroglial water flux and drives the clearance of interstitial solutes and fluid from the brain parenchyma. From here, solutes and fluid may be dispersed into the subarachnoid CSF, enter the bloodstream across the postcapillary vasculature, or follow the walls of the draining veins to reach the cervical lymphatics.