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Table 4 Comparison of properties of the blood–brain barrier and the choroid plexuses

From: Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles

Topic

Blood–brain barrier

Section or ref.

Choroid plexus

Section or ref.

Principal roles

Exclusion of unwanted substances, retention of required substances, rapid transfers of O2, CO2 and regulated transfers of metabolites and wastes

1

Secretion of CSF excluding unwanted substances

1

Nature of barrier

 Location

Wall of microvasculature distributed throughout brain and spinal cord

 

Discrete entities one protruding into each ventricle

 

 Cell types contributing to barrier function

Endothelial cells exposed directly to blood but surrounded on parenchymal side by basement membrane, pericytes and astrocyte endfeet

1, 4, 5

Epithelial cells exposed directly to CSF. Adjacent stroma and capillary wall provide only a small transport barrier

1, 3

 Connections between cells

High resistance tight junctions containing claudin 5 between endothelial cells that greatly restrict paracellular transport

4.34

Low resistance “leaky” tight junctions containing claudin 2 between epithelial cells; underlying peripheral-type, leaky blood vessels

3.4.2, 3.6.4

 Surface area

Various estimates, 50–240 cm2 g−1. Smith and Rapoport [261] quote 140 cm2 g−1

[261, 531533]

Similar to area of blood–brain barrier. Highly folded at both subcellular and cellular levels to fit into the ventricles

[1, 2]

 Ratio of cell membrane area to length of tight junction band around the cell

Relatively small compared to choroid plexuses. Cell surfaces are not folded

4.4

Relatively large compared to blood–brain barrier. Apical brush border and highly folded basolateral membrane

4.4

 Blood flow

0.54 ml g−1 min−1 (but variable, see below)

[534]

Three to ten fold larger than for blood-flow at the blood–brain barrier

2

 Percentage of cerebral blood flow

~99%

2

~1%

2

 Barrier type

High resistance and low permeability to highly polar substances (e.g. mannitol, sucrose). Permeability increases with lipid solubility

 

Classic leaky epithelium producing a high volume of nearly isosmotic fluid transport

 

Transfers related to metabolism

 

 O2 and CO2 transfers

Very rapid. At least partly blood-flow limited. Neurovascular coupling to ensure adequate blood flow to regions with high metabolism

2.3

Presumed to be rapid. Total transfers to and from brain much less than across blood–brain barrier because much less blood flow

2.3

 Glucose transfer

Rapid transport across barrier, extraction of ~30% of that arriving in blood. Passive via GLUT1 in luminal and abluminal membranes. K m close to normal [glucose]plasma which limits excessive entry during raised [glucose]plasma

2.4.1 and see also footnote 1

Total amount transferred small compared to that across the blood–brain barrier. GLUT 1 transporters present in basolateral membrane, but far fewer in apical membrane

2.5

 Lactic acid transfer

Rapid, but saturable, passive transport via MCT1 in luminal and abluminal membranes

6, 6.3

Existence of transepithelial transport unclear. MCT3 present but only in the basolateral membrane.

[535]

 Amino acid transfers

Selective transport via multiple transporters. Concentration in ISF ~1/10th that in plasma. Passive transporters on both sides and Na+-linked transporters on abluminal side maintain this gradient. Amounts transported imply that the Na+ transfer via this route likely to exceed the net transfer of Na+ in any fluid secretion

2.4.2

Same types of transporters as at blood–brain barrier with Na+-linked transporters in the apical membrane, but total amount of amino acids transferred much less than at the blood-brain barrier

2.5

 Vitamins and “micronutrients”, e.g. folate

Minor route of transport

[2, 137]

Major route of transport into brain

3.1, [2, 137]

Transfers related to fluid secretion and regulation of [K+] and [HCO3 ]

 Fluid secretion rate

Unknown. On present knowledge could be anywhere between small net absorption and net secretion comparable to ~50% of CSF production by choroid plexuses. Ion transporters needed are present, so net movement unlikely to be zero. If secretion rate is large, a large portion of ISF must be returned to blood without first mixing with CSF in the cisterna magna

4.1

350–400 ml day−1

3.2

 Water permeability

Sufficient to allow a close approach to osmotic equilibrium between brain and blood. Most water from blood crosses the barrier in a single-pass through microvessels, some via the lipid bilayers of the cell membranes, some possibly via membrane proteins, e.g. GLUT1, some possibly paracellular. Aquaporins absent in endothelium, but AQP4 present on astrocyte endfeet

2.1, 4.3.6

High. Some via AQP1 in apical membrane of epithelium and possibly GLUT1 in basolateral membrane. Some via paracellular route

2.1, 3.4.2

 Na+ transporters

Abluminal: Na+, K+-ATPase (most), Na+-linked transporters, e.g. for amino acids, NHE (some) and possibly NBCe1. Luminal: NKCC1, NBCn1, NDCBE-like, Na+, K+-ATPase (some), NHE (most) and possibly NBCe1

4.6.1 and Figs. 17 and 18

Apical: Na+, K+-ATPase, NKCC1, NBCe2, NHE1 (nearly silent at normal pH?).

Basolateral: NCBE/NBCn2, (NBCn1?)

3.6.1, 3.6.11 and Fig. 6, [4]

 Na+ tracer influx, blood towards brain

~3.4 × 10−5 cm3 s−1×[Na+]plasma in rats, possibly mainly paracellular

4.3.2 and 4.3.4

~3.8 × 10−5 cm3 s−1×[Na+]plasma in rats

4.3.2

 Na+ tracer efflux, brain towards blood

Similar to rate of influx

Footnote 13, 4.3.2, 4.3.5

Smaller than influx

3.6.1 and footnote 6

 Na+ net flux

Unknown, see entry Fluid secretion rate

 

~ 0.15 mol l−1 × 400 ml day−1 = ~0.69 µmol s−1

 

 Cl transporters

Luminal: NKCC1, NDCBE-like?

Unknown sidedness: AE2, anion channels

4.4.2, 4.6.2

Apical: KCC4, NKCC1 and probably anion channels.

Basolateral: AE2 and KCC3.

Figure 5; 3.6.2

 K+ transporters

Abluminal: Na+, K+-ATPase (most)

Luminal: NKCC1 and Na+, K+-ATPase (some)

Both: K+ channels

4.4.1 and 4.5.3

Apical: Na+, K+-ATPase, KCC4, NKCC1 and K+ channels.

Basolateral: KCC3

3.6.4

 Contribution to [K+]ISF regulation

Major

4.3.1, 5, 5.2, 5.3

Minor

3.6.4, 5.1

 K+ fluxes, trans- vs. para-cellular

Amount transported substantially greater than at choroid plexuses. Mainly transcellular

4.3.1, 4.3.4 and 5.2

Transcellular net efflux from CSF and paracellular net influx into CSF

3.64

 K+ tracer influx to brain, acute changes in [K+]plasma

Increased with increased [K+]plasma

5.2

Increased with increased [K+]plasma

5.1

 K+ tracer influx to brain, chronic changes in [K+]plasma

Influx independent of [K+]plasma. Downregulation of luminal transporters with increased [K+]plasma, possibly NKCC1? Upregulation of luminal K+ channels?

5.2, [361]

Influx not increased by increasing [K+]plasma. Unknown mechanism

5.1, [361]

 K+ tracer efflux from brain

Rate varies sigmoidally with [K+]ISF, transport via Na+, K+-ATPase in abluminal membrane

4.3.1

Presumably sigmoidal variation as at blood–brain barrier

 

 HCO3 transporters

NBCe1, NBCn1, AE2, NDCBE-like?, localization not known

4.4.2

Apical: NBCe2

Basolateral: AE2, NCBE/NBCn2

Figures 5 and 6, 3.6.2

 Rate of HCO3 transport

Controversial, fast vs. slow. Balance of evidence now strongly favours slow

6.4.2

~25 mM × 400 ml min−1 = 10 mmol min−1

6.4.1

 Modulation of HCO3 transport by pCO2

HCO3 influx may be increased by increases in [HCO3 ]plasma or pCO2. Increased [HCO3 ]plasma leads to increased pHISF in advance of changes in pHCSF

6.4.2

[HCO3 ] in the secretion changes in the same direction as pCO2

6.4.1

 Importance for regulation of pHISF

Major via regulation of [HCO3 ]ISF

6.4

Unclear

6.4

  1. Numerical values are scaled to be appropriate for an adult human with a 1.4 kg brain unless stated otherwise