cerebral blood flow

Question 1

why is there a BBB

Answer 1

activity of neurones is highly sensitive to composition of local environment; CNS must be protected from fluctuations in composition of blood (homeostasis key for brain)

Question 2

what level is BBB

Answer 2

level of CNS capillaries

Question 3

types of capillaries and relative leakiness

Answer 3

continous (moderate), fenestrated (leaky), sinusoid (very leaky)

Question 4

normal exchange across capillary wall: amount and mode

Answer 4

most plasma leaks out of blood vessels every 9 hours through pores/clefts between endothelial cells

Question 5

when does vessel BBB properties increase

Answer 5

in deeper vessels

Question 6

vessel BBB property (junctions) and reason

Answer 6

extensive tight junctions at endothelial cell-cell contacts, massively reducing solute and fluid leak across the capillary wall

Question 7

cardiac muscle capillary vs brain capillary

Answer 7

both continuous, but brain capillary has very little transcellular vesicular transport

Question 8

interendothelial junctions: peripheral capillaries vs BBB capillaries

Answer 8

number of tight junctions between endothelaial cells, so clefts are more restricted

Question 9

peripheral capillaries vs BBB capillaries: pericyte coverage and astrocytes

Answer 9

dense pericyte coverage in BBB capillaries (pericytes maintain capillary integrity and function), more astrocytes also

Question 10

significance of tight junctions and specific membrane transporters in BBB capillaries

Answer 10

control exchange of hydrophilic substances e.g. glucose, amino acids, some antibiotics and toxins etc.

Question 11

effect of BBB on blood-borne infectious agent entry to CNS tissue; impact of loss of BBB

Answer 11

reduced; can help with clearing some infections by allowing immune cells access

Question 12

how do lipophilic molecules cross BBB into CNS

Answer 12

passive diffusion down concentration gradient

Question 13

how do hydrophilic substances cross BBB into CNS (water, glucose, amino acids, electrolytes)

Answer 13

water: aquaporin (AQP1, AQP4) channels; glucose: GLUT-1 transporter proteins; amino acids: 3 different transporters; electrolytes: specific transporter systems

Question 14

principal feature of circumventricular organs

Answer 14

close to ventricles with capillaries that lack BBB properties

Question 15

characteristics of capillaries and ependymal cells in circumventricular organs

Answer 15

leaky, fenestrated capillaries but tighter ependymal lining, so sample plasma, allwoing but limiting exchange into CSF

Question 16

2 examples of circumventricular organs and function

Answer 16

posterior pituitary and median eminence; secrete hormones

Question 17

function of circumventricular organ area postrema

Answer 17

samples plasma for toxins, inducing vomiting

Question 18

other functions of other circumventricular organs

Answer 18

sensing electrolytes, regulate water intake

Question 19

when does BBB break down (4 cases)

Answer 19

inflammation, infection, trauma, stroke

Question 20

clinical importance of BBB in pharmacology

Answer 20

entry of drug into brain (good or bad)

Question 21

effect of “old-fashioned” antihistamine H1 blockers on BBB

Answer 21

hydrophobic so could cross BBB by diffusion, making people drousy (sold as sleep aids)

Question 22

effect of second-generation antihistamine H1 blockers on BBB

Answer 22

polar so do not readily cross BBB and cause drowsiness

Question 23

how can Parkinson’s disease be treated, and impact of BBB

Answer 23

elevated dopamine levels in brain, but dopamine cannot cross BBB

Question 24

what is used to allow dopamine into the brain

Answer 24

prodrug L-DOPA can cross BBB via amino acid transporter, then converted to dopamine in brain by DOPA decarboxylase

Question 25

problem with using L-DOPA to treat Parkinson’s disease, and solution

Answer 25

most converted to dopamine peripherally, so less available to access brain; co-administered with carbidopa which inhibits DOPA decarboxylase, but cannot cross BBB, so doesn’t affect conversion of L-DOPA to dopamine in brain