Blood brain barrier

Question 1

Quantify blood flow to the brain

Answer 1

55ml/100g tissue/min

15% of cardiac output and 20% of oxygen consumption whilst it only take up 2% of the body weight

Question 2

What happens when blood flow to brain reduced by more than 50%?

Answer 2

insufficient oxygen delivery
function significantly impaired

Question 3

what is syncope? and what are its causes?

Answer 3

syncope = fainting
a manifestation of reduced blood supply to the brain
causes include: low bp, vago-vasal attack, sudden pain, emotional shock, postural changes
all result in temporal interruption or reduction of blood flow to brain

Question 4

what can’t the brain do?

Answer 4

synthesise, utilise, or store any other source of enerfy apart from glucose

Question 5

under what threshold, if glucose falls does unconsciousness, coma and death result?

Answer 5

2mM

normal fasting levels (4-6mM)

Question 6

in which two broad ways is cerebral blood flow maintained?

Answer 6

1) mechanisms affecting total cerebral blood flow

2) mechanisms which relate activity to the requirement in specific brain regions by altering local blood flow

Question 7

between which MABPs is total CBF autoregulated?

Answer 7

between 60 -160 mm Hg, total cerebral blood flow is autoregulated

Question 8

how is total CBF autoregulated?

Answer 8

stretch sensitive cerebral vascular smooth muscle in the arteries/arterioles contracts or dilates at high BP and low BP respectively

if BP rises above 160 mm Hg, there is too much blood flow which results in swelling of brain tissue, and increased intracranial pressure which is dangerous

Question 9

why is local autoregulation required?

Answer 9

local brain activity determines local glucose and oxygen demands so local changes in blood supply required
therefore local autoregulation required

Question 10

in which two ways is local autoregulation of cerebral blood flow conducted?

Answer 10

1) neural control

2) chemical control

Question 11

what is the patterns of vascularisation in the CNS tissues?

Answer 11

arteries enter the CNS tissue as branches of the surface pial vessels. These penetrate through the brain parenchyma and branch to form capillaries. These drain into venules and veins which drain into surface pial veins

Question 12

how close is each neurone to a capillary?

Answer 12

No further away than 100 micrometers from a capillary

Question 13

4 neural factors that contribute to local autoregulation?

Answer 13

1) sympathetic nerve stimulation to main cerebral arteries producing vasoconstriction - this only operates when arterial BP is high
2) parasympathetic nerve stimulation from facial nerve producing slight vasodilation
3) central cortical neurones releasing a variety of vasoconstrictor NTs like catecholamines (adrenaline/noradrenaline)
4) dopaminergic neurones producing vasoconstriction

Question 14

what are pericytes?

Answer 14

pericytes are cells that wrap around capillaries and have diverse activities like immune function, transport properties, contractile

Question 15

how do dopaminergic neurones contribute to local autoregulation?

Answer 15

innervate penetrating arterioles and pericytes around capillaries.
they may participate in the diversion of cerebral blood to areas of high activity
dopamine may cause contraction of pericytes via aminergic and serotoninergic receptors

Question 16

list some chemical factors that contribute to local autoregulation?

Answer 16

1) C02 (indirectly) and pH
2) NO
3) K+
4) adenosine
5) anoxia
6) kinins, prostaglandins, endothelins

ALL ABOVE ARE VASODILATORS

Question 17

what is the effect of pCO2 on CBF? and how does it do this?

Answer 17

increases CBF
CO2 from blood or from local metabolic activity generates H+ using carbonic anhydrase in surrounding neural tissue and in the smooth muscle cells
the elevated H+ decreases the pH which causes relaxation of the contractile smooth muscle cells, dilation of the vessels resulting in increased blood flow

Question 18

what can increased blood flow be equated to in the CNS?

Answer 18

increased neuronal activity

Question 19

where is CSF produced?

Answer 19

in regions of choroid plexus in the cerebral ventricles

Question 20

what are ependymal cells?

Answer 20

these are epithelial-like glial cells which are often ciliated and they line ventricles, aqueducts and canals of the brain

Question 21

what is the choroid plexus?

Answer 21

a modified ependymal lining which results in the formation of branched villus structures

Question 22

How is CSF formed?

Answer 22

1) capillaries leaky but local ependymal cells have extensive tight junctions
2) secrete CSF into ventricles ( lateral ventricles -> 3rd ventricle via interventricular foramina -> 4th ventricle via cerebral aqueduct and then into subarachnoid space via medial and lateral apertures)
this circulates around

Question 23

Volume of CSF

Answer 23

80-150mL

Question 24

functions of the CSF

Answer 24

protection (physical and chemical), nutrition of the neurones, transport of molecules

Question 25

main differences between the plasma and CSF

Answer 25

1) CSF contains little protein
2) CSF contains much more Mg++
3) CSF contains much less Ca++

Question 26

why is a BBB required?

Answer 26

activity of neurones is highly sensitive to composition of local environment and the CNS must be protected from the fluctuations in the composition of blood

Question 27

what is the BBB formed from?

Answer 27

the capillaries of CNS parenchyma derived from surface pial vessels

BBB properties increase the deeper u go
BBB capillaries have extensive tight junctions at the endothelial cell-cell contacts, massively reducing solute and fluid leakage across the capillary wall

Question 28

more differences between peripheral and BBB capillaries?

Answer 28

1) peripheral vessels have sparse pericyte coverage whereas BBB capillaries have dense pericyte coverage
2) BBB capillaries are covered with end-feet from astrocytes which is important for maintaining BB properties

Question 29

how are hydrophilic substances supposed to cross the BBB?

Answer 29

1) water via aquaporin (APQ1, APQ4) channels
2) glucose via GLUT1 transporter proteins
2) amino acid via 3 different transporters
4) electrolytes via specific transporter systems

Question 30

in which areas is it necessary for capillaries to lack BBB properties?

Answer 30

circumventricular organs (CVOs) which are areas found close to the ventricles

Question 31

what are CVOs characterised by and give examples of CVOs?

Answer 31

CVOs have fenestrated capillaries - to compensate the local ependymal lining is much tighter than in other areas to limit exchange between them and the CSF.

examples of CVOs include:

1) posterior pituitary and median eminence which secrete hormones
2) area postrema which samples plasma for toxins and induces vomitting

Question 32

when does the BBB break down?

Answer 32

inflammation, trauma, infection, stroke

Question 33

significance of anithistamines and BBB?

Answer 33

old-fashioned anitistamines (H1 blockers) were hydrophobic and could cross the BBB by diffusion this resulted in drowsiness and histamine is important in wakefulness and alertness
newer antihistamines are polar (they have a hydrophilic attachment) so do not cross BBB and do not cause drowsiness

Question 34

how does the BBB affect the treatment of Parkinson’s disease?

Answer 34

dopamine cannot cross BBB
so L-Dopa (precursor) given which can cross the BBB via and AA transporter bc it has a similar strtucture to an amino acid and is converted to dopamine in the brain using DOPA decarboxylase
To inhibit conversion of L-Dopa to dopamine outside the brain it is co-adminstered with DOPA decarboxylase inhibitor, Carbidopa, which cannot cross the BBB so does not affect the conversion of L dopa in the brain