Vessel Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 362

clefts more effectively than in other endothelia; 25 (2) absence of interstice, except in
the hypothalamic-pituitary axis; 26 and (3) astrocyte extensions 27 that surround the
capillary endothelium. Astrocytes provide the cellular connection to the neurons.
Therefore, transit across the blood-brain barrier involves transport successively
through the endothelium wetted membrane, cytoplasm, antiluminal membrane,
basement membrane, and astrocyte extension.
The endothelium forms functional neurovascular units with astrocytes and
neurons characterized by strongly regulated blood-brain barrier functioning. The
distance between any neuron and brain capillary usually is lower than 20

m. 28 The
brain endothelium supplies the brain with essential nutrients and mediates efflux of
waste products. Specific ion carriers regulate ionic motions to produce appropriate
brain interstitial fluid, avoiding damaging fluctuations in ionic composition, and
then disturbances in axonal signaling.
Biochemical bridges exist between the endothelium and astrocytes. Basal lam-
inae of cerebral capillaries contain agrin . This heparin sulfate proteoglycan binds
to - dystroglycan , a member of the dystrophin-dystroglycan complex that links

to aquaporin-4 of astrocyte extension via

α

α - syntrophin , another member of the

dystrophin-dystroglycan complex. α -Syntrophin also binds to the K IR 4.1 channel

of astrocyte extension.
Astrocytes, pericytes, perivascular macrophages, and neurons regulate BBB
features, such as tight junction properties, endothelium polarity, and enzymatic
activity. Astrocyte-derived factors, such as transforming growth factor- , glial-

derived neurotrophic factor, basic fibroblast growth factor, and angiopoetin-1 can act
on endothelial receptors [ 667 ]. Conversely the endothelium acts on the growth and
differentiation of perivascular cells, particularly via endothelium-derived leukemia
inhibitory factor.
Cell interactions occur not only for development, but also for functioning modu-
lation. Astrocytes, after sensing neuronal cues, can send signals to the capillaries to
supply nutrients, using inositol (1,4,5)-trisphosphate, glutamate, and ATP through
gap junctions or via receptor stimulation. Moreover, water and ions are redistributed
between the components of the functional neurovascular units.
Active neurons release neurotransmitters and K + and take up Na + . They generate
water during glucose metabolism. Neurotransmitters and ions are mostly recycled.
The perivascular space acts as a K + space buffer for recycling, as the astroglial

β

25 The brain tight junction restricts even the movement of small ions such as Na + and Cl − ions.
26 The hypothalamus, above the pituitary gland, or hypophysis, is located in the middle of the base
of the brain, encapsulating the ventral portion of the third ventricle. The hypothalamus controls
many body functions. The anterior pituitary (adenohypophysis) secretes protein hormones, under
control by hypothalamic hormones. The posterior pituitary (neurohypophysis) is an extension of
the hypothalamus. They release several hormones controlling endocrine gland function.
27 Astrocyte extensions facing the capillary wall have peculiar features, such as high density of
patches with aquaporin-4 and K IR 4.1 channels, that are involved in ion and volume regulation.
28 The distance between a neuron and cerebrospinal fluid is on order 1 millimeter or even
centimeter.