Week 1 BBB and Metabolism- Drewes

Question 1

List possible pathways between blood and brain

Answer 1

Lipophillic
Transmembrane transporters
Efflux pumps (P-glycoprotein)
Transcytosis
Immunce cell migration (diapedesis)

Question 2

Paclitaxel transport

Answer 2

• usually does not cross BBB
• attached substance that binds to LRP-1 (Receptor for transcytosis)
• Trojan horse approach

Question 3

How do white blood cells get into brain?

Answer 3

-DIAPEDISIS
-Lymphocytes roll with weak adhesion to endothelial cell
-Roll along
-Additional adhesion (strong)
-enter brain
-enhance by chemokines- cause adhesion molecules to become more expressed
(contributes to MS)

Question 4

At what time does the BBB form?

Answer 4

First few weeks after fertilizaiton

Question 5

What does MCT1 transport? and is it expressed more in adults or babies?

Answer 5

Transports lactate and ketones, more highly expressed in babies

Question 6

What is the significance of the P-glycoprotein?

Answer 6

• One of several efflux transporters
• pumps out anti-cancer, anti-epilepsy and therapeutics
• Prevents them from reaching their target!

Question 7

What is imported into the brain via transcytosis?

Answer 7

• Insulin, transferrin, albumin, other plasma proteins
• Paxlitaxel utilized this method via the “trojan Horse” approach
• Attach paclitaxel to a moleucle that binds to LRP-1 receptor
• Binding induces transcytosis

Question 8

What is the glymphatic system?

Answer 8

• supports interstitial fluid and solute clearance from the brain
• Fluxes of CSF and ISF propel the waste products of neuron metabolism, into the para-venous space, then directed into lymphatic vessels

Question 9

what is the physical “blood brain barrier”

Answer 9

tight junctions that form between the endothelial cell lining the capillary

Question 10

What proteins are involved in the tight junctions between endothelial cells lining the capillary?

Answer 10

Claudin
JAM (junctional adhesion molecule)
Occludin

Question 11

What are the inner and outer membranes of the capillary called?

Answer 11

Luminal (inside)

Abluminal (outside)

Question 12

What MCT-1?

Answer 12

-12 transmembrane segments -transport lactate, pyruvate, acetate, butyrate and ketones-either direction, down concentration gradient-more MCT-1 expressed in neonates

Question 13

What is the equation for determining brain consumption of substrates?

Answer 13

CMR-G = (A-V)F/W

A= arterial conc. (mol/l)
V= arterial conc. (mol/l)
F= blood flow (l/min)
W= weight (g)
CMR Unites= moles/g/min

Question 14

Stoichiometery for glucose and oxygen metabolism in brain?

Answer 14

One glucose for every 6 oxygen

Note: if doesn’t add up perfectly, rest of glucose is getting converted to lactate

Question 15

What is happening CMR of G and O in:
Epilepsy
Drowning/Hypoxia
Alzheimers
Anestetic

Answer 15

Epilepsy- both increase
Hypoxia- O lower, G higher because rate of glycolysis is increasing
Alzheimers- both decrease
Anestetic- both decrease

Question 16

Why is deoxy-glucose useful?

Answer 16

Analog of glucose that is transported into cells but cannot be degraded that is radio active

-use to see energy demands in brain

(eyes open vs. eyes shut vs one eye open)