Biomedical Engineering Reference
In-Depth Information
mammalian brain from potentially harmful compounds in the blood. It is a
selectively permeable, hydrophobic barrier that is readily crossed by small,
lipid-soluble molecules. It serves not only to restrict entry of toxic polar
molecules into the brain but also as a regulatory system that stabilizes and
optimizes the fluid environment of the brain's intracellular compartment. A
dysfunctioning BBB allows influx of normally excluded hydrophilic molecules
into the brain tissue. This might lead to cerebral edema, increased intracranial
pressure, and, in the worst case, irreversible brain damage.
The BBB is an anatomic/physiological complex associated with the cere-
bral vascular system. It is composed of a network of astrocytic pseudopodia
which envelops the tight junctions of the vascular endothelium. It is a natural
defense system that maintains the physiochemical environment of the brain
within certain narrow limits that are essential for life. It functions as a differ-
ential filter that permits the selective passage of biological substances from
blood to brain. For instance, amino acids, anesthetics, and glucose may gain
access to brain cells, while carbohydrates, proteins, and most microorganisms
and antibiotics are excluded from brain tissues by the BBB. Uninten-
tional opening of the BBB may subject the CNS to assault from extraneous
microorganisms.
This selective permeability has the disadvantage that agents and drugs that
are effective in treating diseases in other parts of the body may not be able to
gain entry into the brain to combat infection. The ability to selectively open
the BBB suggests the possibility of using microwave regional hyperthermia to
facilitate chemotherapy for brain tumors and facilitate the delivery of anti-
cancer drugs such as methotrexate. This substance is the drug most often used
for high-dose chemotherapy, with BBB permeability; however, it is among the
lowest of the agents currently used clinically and is normally excluded from
the brain.
About 30 investigations on the effect of microwave radiation on BBB per-
meability were reported until 2002 [41]. The assay methods employed include
visual dye markers,
such as Evans blue,
sodium fluorescein,
and
rhodamine-ferritin
radioactive tracers
horse radish peroxidase and electron microscopy
endogenous albumin.
Visual dye markers are very easy to use. This is, however, a qualitative method.
Radioactive tracer methods offer a quantitative analysis.
Among these investigations, the studies showing increased BBB perme-
ability in experimental animals are about equal in number with those that do
not report BBB disruption at high as well as at low SARs. Some of the appar-
ent discrepancies undoubtedly stemmed from the complexity of the BBB and
from differences in microwave exposure conditions, such as frequency power
level and SAR distribution, and from differences in the use of a variety of
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