Biomedical Engineering Reference
In-Depth Information
able to metabolize peptides and ATP, respectively. Intracellular enzymes such as
monoamine oxidase and cytochrome-P450 can inactivate many neuroactive and
toxic compounds. Renin, angiotensin-converting enzyme, and aminopeptidase-A
acting on angiotensin belong to degrading enzymes of the blood-brain barrier.
Certain substances that are not carried by the endothelium, are metabolized in
endothelial cells such that they cannot enter into the brain. The cerebral endothelium
has enzymes that mainly target neuroactive substances, found in low concentration
or absent in other capillaries.
7.4.1.1
Intracellular Permeability
The luminal and abluminal membranes of brain capillaries differ chemically and
functionally. Asymmetrical distribution of carriers is observed between luminal
and abluminal membrane regions, due to amount difference or absence (transport
polarity).
Small gaseous molecules such as O
2
and CO
2
can diffuse freely through the lipid
membranes, as well as small lipophilic agents. Specific carriers on the luminal and
abluminal membranes regulate transcellular transport. The endothelium contains
carriers for glucose, amino acids (such as bidirectional L systems for large neutral
amino acid transporter LAT1, or SLC7a5), purine bases, nucleosides, choline, and
other substances. Efflux carriers depend on available energy.
Whereas alkaline phosphatase activity is located in both the luminal and
antiluminal cytoplasmic membranes of brain capillary endothelial cells, the K
+
-
dependent phosphatase activity associated with Na
+
-K
+
ATPase resides only in
the abluminal membrane [
672
]. The main glucose carrier isoform GluT1 at BBB
that is bidirectional, has a 1:4 ratio of luminal-abluminal distribution [
673
]. Na
+
-
dependent glutamate
19
carriers, such as excitatory amino acid transporters EAAT1
to EAAT3 that allow glutamate efflux against concentration gradient, are mostly
abluminal.
7.4.1.2
Extracellular Permeability - Tight Junctions
Tight junctions (or zonula occludens), in combination with ubiquitous adherens
junctions, form junctional complexes that restrict the paracellular permeability
of the brain capillary wall. Tight junctions separate cell membranes into apical
and basolateral regions. Tight junctions are indeed characterized by completely
occluded areas between external membrane sheets of adjoining cells.
19
Glutamate is a cerebral excitatory transmitter. Astrocytes recycle glutamate. Glutamate influx
occurs particularly via excitatory amino acid transporter-1 and -2 is followed by conversion into
glutamine to be taken by adjoining neurons.
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