Vessel Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 363

plasma membrane has a high density of K + carriers on its perivascular extension.
Astrocyte extensions particularly possess inwardly rectifying K IR 4.1 channels,
Na + -K + AT P a s e , a n d N a + -K + -Cl − cotransporters (SLC12a1-SLC12a2). The
cerebral endothelium has a low K + and water permeability. Excess water is removed
from the perivascular spaces, using lymph and cerebrospinal fluid.
Activated protein-C is a serine peptidase with anticoagulant, 29 anti-inflammatory,
and cytoprotective activity 30 that crosses the blood-brain barrier via endothelial
protein-C receptor to fulfill its neuroprotective effect [ 676 ]. 31 Its interaction on the
endothelium is needed, as the protein-C precursor is not synthesized or at very low
amount in the central nervous system. It is conveyed by blood down to the brain. Its
transfer from blood requires not only its binding to endothelial protein-C receptor,
but also activation of peptidase-activated PAR 1 receptor.

7.4.3 Functional Hyperemia

Blood flow is locally increased in active cerebral regions. Neural activity consumes
energy ( functional hyperemia ). Neural activity cues are transmitted to the vascu-
lature by astrocytes. During neuronal activity, glutamate released by the neuron
activates glutamate receptors of the astrocyte plasma membrane and triggers a
calcium wave. Calcium ions reach the vascular extension of the astrocyte, where
they stimulate phospholipase-A2 for arachidonic acid production. Arachidonic acid
is then metabolized by cyclooxygenase COx1 32 into a prostaglandin vasodilator
PGe2 (Fig. 7.6 )[ 675 ]. Enzyme COx1 that is highly expressed in astrocyte vascular
endfeet is the main mediator of astrocyte-induced vasodilation. Moreover, Ca 2 +
stimulates production of inositol trisphosphate that crosses gap junctions and
triggers calcium motions and prostaglandin synthesis in neighboring astrocyte
extensions that ensheath the vessel wall.

29 Anticoagulant activity of activated protein-C is done by irreversible inactivation of coagulation
factors FVa and FVIIIa.
30 Anti-apoptotic and anti-inflammatory activity of activated protein-C requires activation of
peptidase-activated receptor PAR 1 .
31 Activated protein-C inhibits neuron death, protects endothelial barriers from injury, and blocks
tissue-plasminogen activator-mediated breakdown of the blood-brain barrier after stroke. Endothe-
lial protein-C receptor binds both protein-C and activated protein-C selectively and saturably.
However, endothelial protein-C receptor has a significantly lower affinity for protein-C than
activated protein-C.
32 Enzyme COx1 is constitutively produceed by astrocytes, whereas COx2 is expressed in response
to inflammatory stimuli.