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Authors:  (InÍs Palmela, Dora Brites, Maria Alexandra Brito, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal)
Abstract:
The blood-brain barrier (BBB) is an elaborate structure of utmost
importance, as it separates the brain compartment and the peripheral organs,
allowing the creation of a unique brain environment for optimal neuronal
activity. Endothelial cells of brain microvasculature present special
properties that restrict the free movement of molecules and are thus
considered as the anatomic basis of the BBB. The presence of both tight and
adherens junctions, together with transporters and intracellular signalling
pathways, actively influence and regulate the barrier properties of these
endothelial cells. Moreover, endothelial interactions with other brain cells
and matrix components are crucial for the maintenance of a proper BBB.
This has led to the concept of neurovascular unit, which embraces the known
and crucial interactions between endothelial cells and astrocytes, pericytes
and the basement membrane, as well as the possible interplay with neurons
and microglia. Additionally, the endothelial cells act as a signalling interface
between the compartments that are separated, being directly activated by
signals from both environments and responding accordingly, therefore
actively participating in brain protection. Although the role of the BBB in the
progression or even as a cause of central nervous system (CNS) disorders has
often been dismissed, it is nowadays believed that BBB dysfunction plays an
important role in the progression of numerous CNS disorders. In fact, it has
recently been documented that disruption of tight junctions occurs in
multiple sclerosis, sepsis, human immunodeficiency virus (HIV) infection
and brain tumours, or even in diseases like Alzheimerís disease, Parkinsonís
disease and epilepsy, in which there is also evidence of transporter
deregulation. A dysfunctional or even disrupted BBB causes a perturbation
of blood-brain homeostasis, with an associated increased infiltration of
immune cells into the brain compartment. These events are ultimately
responsible for the exacerbation of brain injury and are thus key players in
disease aggravation. In this chapter, the unique properties of the BBB are
explored in order to better understand the role of this complex structure in
brain homeostasis. Furthermore, it is intended to increase the awareness of
the importance of studying this dynamic structure, as it can be an important
player in the progression of CNS disorders. 


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Blood-Brain Barrier in Health and Disease (pp.65-88)