Chemistry Reference
In-Depth Information
FIGURE 20.6
The cell associations at the BBB. The cerebral endothelial cells form tight junctions at their margins which seal the aqueous
paracellular diffusional pathway between the cells. Pericytes are distributed discontinuously along the length of the cerebral capillaries and
partially surround the endothelium. Both the cerebral endothelial cells and the pericytes are enclosed by, and contribute to, the local basement
membrane which forms a distinct perivascular extracellular matrix (basal lamina 1, BL1), different in composition from the extracellular matrix
of the glial end-feet bounding the brain parenchyma (BL2). Foot processes from astrocytes form a complex network surrounding the capillaries
and this close cell association is important in induction and maintenance of the barrier properties. Axonal projections from neurons onto
arteriolar smooth muscle contain vasoactive neurotransmitters and peptides and regulate local cerebral blood. BBB permeability may be
regulated by the release of vasoactive peptides and other agents from cells associated with the endothelium. Microglia are the resident
immunocompetent cells of the brain. The movement of solutes across the BBB is either passive, driven by a concentration gradient from plasma
to brain, with more lipid-soluble substances entering most easily, or may be facilitated by passive or active transporters in the endothelial cell
membranes. Efflux transporters in the endothelium limit the CNS penetration of a wide variety of solutes.
(From
Abbott et al., 2009
. Copyright
2009 with permission from Elsevier.)
with microglia and the oligodendrocytes, are the major cell type in the central nervous system. The network
of astrocytic processes forms the infrastructure on which all other CNS cells and vessels are anchored. They
have a multitude of functions, including regulation of the ionic milieu in the intercellular space, uptake and/or
breakdown of some neurotransmitters, supplying nutrients to the neurons, and formation of the blood
brain
barrier. Microglia are also found in the vicinity of the BBB. The microglia are the resident macrophages of the
central nervous system, which can communicate with the astrocytes and neurons and with cells of the immune
system by a large number of signalling pathways. They are the most susceptible sensors of brain pathology, and
when they detect any signs of brain lesions or nervous system dysfunction, they undergo a complex, multistage
activation process that converts them into the “activated microglia.” Activated microglial cells have the capacity
to release a large number of substances that can act detrimentally, usually causing inflammation, or sometimes
beneficially upon surrounding cells; they can also move to the site of injury, proliferate, and phagocytose cells
and cellular compartments.
e
SODIUM, POTASSIUM, AND CALCIUM CHANNELS
Nerve impulses consist of a wave of transient membrane depolarisation/re-polarisation which traverses the nerve
cell and is designated an action potential. As we saw in Chapter 9, Alan Hodgkin and Andrew Huxley demon-
strated in 1952 that a microelectrode implanted into the giant axon (the long process emanating from the body of
