Page 49 - Human Lyme Neuroborreliosis

The Blood-brain Barrier 33

subsets of leukocytes. There are two routes for leukocytes to pass through
endothelial cell, the so called paracellular route, or through the endothelial cell
itself or transcellular route. The BBB with its abundance of TJ complexes
relies primarily on the transcellular route as it does for solute and fluid
transport. Neutrophil recruitment is partially dependent ICAM-1, and express
L-selectin and lymphocyte function-associated antigen (LFA)-1 but not
chemokine C motif receptor 7 (CCR7) may explain why granulocytes roll but
do not arrest for transmigrate in high endothelial venules (HEV).

Pericyte Interactions

Brain endothelial cells are exposed to a myriad of pericyte interactions
[42] in the regulation of brain angiogenesis, endothelial cell TJ formation, as
well as the differentiation, microvascular vasodynamic capacity, structural
stability, and neuroimmunologic network operations of the intact BBB [43].
Rouget [44] first ascribed capillary contractility to pericytes but Zimmermann
named the cell and described its morphologic aspects [45]. The presence of
smooth muscle cells in association with pericytes and the absence of a smooth
muscle layer from capillaries and postcapillary venues influenced early views
ascribing contractile properties to narrow capillaries hence regulate
microvascular flow even though a number of subsequent experimental studies
failed to substantiate it [46, 47]. Smooth muscle actin was conclusively
demonstrated in pericytes by immunocytochemistry employing smooth muscle
?-actin isoform specific antibodies and immunogold labelling in conjunction
with electron microscopy noting that smooth muscle ??actin expression in
capillaries was limited exclusively to pericytes and not present in endothelial
cells [48]. Since the histochemical localization of smooth muscle ?-actin is
demonstrated in precapillaries and not in midcapillaries, it has been suggested
that smooth muscle ?-actin containing capillaries are involved in contractility
and the control of capillary blood flow in the BBB [49].

Unlike other perivascular cells that lie within the microvessel basal lamina
and contribute to its formation, typical CNS pericytes are flattened or
elongated stellate-shaped solitary cells with multiple cytoplasmic processes
encircling the capillary endothelium and contacting a large abluminal vessel
area. Brain pericytes are characterized by granular deposits present in
lysosomes that strongly react with acid phosphatase, a finding that led to
consideration of a phagocytic role [50]. They rapidly phagocytose an
intravenous injection of HRP which can be employed as a pericyte

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