Hello. This is Martha O'Donnell of
the Department of Physiology and Membrane Biology at the University of California, Davis.
I will discuss what we know about blood-brain barrier ion transporters and channels,
and the role that they play in water and electrolyte homeostasis of the brain,
both in health and disease.
I will begin with an overview of the blood brain-barrier and talk about
the role of the barrier in water and electrolyte homeostasis of the brain.
Next, I will turn to a discussion of
the ion transporters and channels that we know are present in the blood-brain barrier,
and talk a bit about how these transporters and channels are thought to participate in
sodium secretion and potassium absorption across the blood-brain barrier.
Finally, in the third section,
I will discuss cerebral edema formation in ischemic stroke,
as an example of how blood-brain barrier transporters contribute to
changes in water and electrolyte distribution in the brain during stroke.
In particular, I will talk about the possible role that
blood brain-barrier sodium transporters play in edema formation during stroke.
And lastly, I will discuss recent studies from my own laboratory,
studies that provide evidence for a role of
blood-brain barrier sodium potassium chloride cotransport
in ischemia-induced edema formation.
Let's begin then with part one,
an overview of the blood-brain barrier with a focus on the barrier's role
in water and electrolyte homeostasis in the brain.
First, it's important to remember that it is
endothelial cells of brain microvessels that comprise the blood-brain barrier.
A barrier that lies between blood and brain.
The electron micrograph shows a brain capillary.
Note here, the capillary lumen and the endothelial cell marked by the arrow.
The cell nucleus can be seen to the right of the capillary lumen.
While the microvessel endothelial cell itself forms the blood-brain barrier,
the abluminal surface of the blood-brain barrier is
ensheathed by foot processes of perivascular astrocytes.
Note that, in the context of blood-brain barrier endothelial cells,
the apical surface is luminal,
that is lumen-facing and the basal lateral surface is abluminal.
The cartoon on the left based on the electron micrograph,
illustrates the end feet more clearly.
A prevalent characteristic of blood-brain barrier
endothelial cells is the presence of complex tight junctions.
These tight junctions create a barrier with very limited paracellular solute flux.
The blood-brain barrier also has very few pinocytotic vesicles.
That is, little vesicular traffic that could move solutes between blood and brain.
This means that the vast majority of solutes must move across
the blood-brain barrier via a transendothelial rather than a paracellular route.
And thus, it is blood-brain barrier transporters
that determine what moves between blood and brain.
In this regard, an important function of the blood-brain barrier is to
regulate the composition and volume of brain interstitial fluid.
While the endothelial cells provide the anatomic blood-brain barrier,