Page 47 - Human Lyme Neuroborreliosis

The Blood-brain Barrier 31

enhanced pericyte coverage in germinal matrix, it remained less than in other
brain regions.

Cellular Elements of the BBB

Endothelial Cell Interactions

The existence of the endothelial cell was first surmised by William
Harvey, first observed by Marcello Malpighi in blood capillaries using
compound microscopy in the nineteenth century, and later by electron
microscopy in the mid-twentieth century, revealing the presence of
plasmalemmal vesicles or caveolae. The ability to culture EC later permitted
even more detailed investigation of their activation and function in vivo.
Derived from mesoderm via the differentiation of hemangioblasts and
angioblasts, there are a few protein/mRNA marker candidates including
platelet/endothelial cell adhesion molecule (PECAM)-1 in monocytes and VE-
cadherin in fetal stem cells. Endothelial cells of the BBB not only provide a
physical barrier between the systemic circulation and the brain, but assure the
selective inward passage of ions, nutrients, and neuropeptides via specialized
transport mechanisms. Sodium, potassium, chloride, hydrogen, bicarbonate
and calcium ions are transported across the BBB via transporters located
mainly along the luminal surface of endothelial cells including, the sodium and
potassium adenosine triphosphate (ATP)-dependent transport pump, the
sodium-potassium-chloride cotransporter (NKCC), sodium-proton, chloride-
bicarbonate, and sodium calcium exchanges that assure optimal levels of brain
electrolyte levels and intracellular pH. The transport of essential nutrients is
assured by members of the soluble carriers (SLC) superfamily, located
variably along the luminal and abluminal membrane including, glucose
transporter-1 (GLUT1), monocarboxylic acid-1 (MCT-1); excitatory, organic
acid (OAT), cation (OAC), amine and choline transporters (CTL1),
respectively to transport lactate and ketone bodies as alternative energy
neuronal sources, and sodium-independent or dependent removal of glutamate,
aspartate, glutamine, histidine, and asparagine from the interstitial
compartment of the brain. Other specific carrier-mediated transporters mediate
the passage of transferrin, low-density lipoproteins, leptin, immunoglobulin G
(IgG), insulin, and growth factors via receptor-mediated transcytosis via
binding of the protein to specific receptors on the endothelial cell surface
following by endocytosis of the ligand-receptor complex with passage across

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