BLOOD-BRAIN
BARRIER
The blood-brain barrier
(BBB) is the cellular interface between the blood and the CNS. It serves to
protect the brain from unwanted intrusion by many large molecules and
potentially toxic substances and to maintain the interstitial fluid environment
to ensure optimal functioning of the neurons and their associated glial cells.
The major cellular basis for the BBB consists of the capillary endothelial
cells which have an elaborate network of tight junctions; these tight junctions
restrict access by many large molecules, including many drugs, to the CNS.
Endothelial cells in the CNS also exhibit a low level of pinocytotic activity
across the cell, providing selected specific carrier systems for the transport
of essential substrates of energy production and amino acid metabolism into the
CNS. Astrocytic end foot processes abut the endothelial cells and
their basement membranes; these processes help to transfer important
metabolites from the blood to neurons and can influence the expression of some
specific gene products in the endothelial cells. These astrocytic processes
also can remove excess K+ and some neurotransmitters from the
interstitial fluid.
CLINICAL POINT
The BBB, anatomically
consisting mainly of the capillary tight junctions of the vascular endothelial
cells, serves to protect the CNS from the intrusion of large molecules and
potentially damaging agents from the peripheral circulation. The neurons need
protection of their ionic and metabolic environment, which is aided by glial
cells and the BBB. There are selected areas (windows on the brain) where the
BBB is not present, such as the median eminence, the area postrema, the organum
vasculosum of the lamina terminalis, and others, and where specialized cells can
sample the peripheral circulation and can initiate corrective brain mechanisms
to protect the neuronal environment. The presence of the BBB presents a
challenge for pharmacotherapy aimed at the CNS; many antibiotics and other
agents will not penetrate the BBB and must be coupled to a carrier molecule
that does cross or must be injected intrathecally. In some pathological
circumstances, such as the presence of a brain tumor, neuronal degeneration
resulting from a neurodegenerative disease, the presence of a high
concentration of a solute, or a stroke, the BBB is disrupted extensively,
exposing the internal CNS milieu to molecules in the peripheral circulation.
Therapeutic strategies now are being tested that will achieve transport of
desired pharmacotherapeutic agents across the BBB and will protect the brain
from unwanted disruption of the BBB in pathological circumstances.
