Aluminum and Blood-Brain Barrier Permeability
by Prof. William A. Banks
http://www.trufax.org/general/aluminum3.html
Aluminum (Al) has specific effects on the functions of the blood-brain
barrier (BBB). The BBB is largely comprised of the capillary bed of the
brain and the choroid plexus and regulates the exchange of substances
between the fluids of the brain (interstitial fluid and cerebrospinal
fluid) and the circulation. The BBB, therefore,
plays key roles in both the nutrition and homeostasis
of the central nervous system (CNS). The BBB also
regulates the exchange between the CNS and the blood of many regulatory
substances such as peptides and so plays a role in the connnunication
between the CNS and peripheral tissues. Most studies have examined the
effects of acute injections of Al. Al does not disrupt the BBB or alter
cerebral blood flow. Al tends to enhance the blood to brain uptake of
water soluble substances that cross the BBB by non-saturable
processes. For example, Al increases the blood to
brain uptake of delta sleep-inducing peptide and beta
endorphin. The degree to which uptake is increased
correlates with the lipid solubility of the substance. Al does not chelate
with the substance, but interacts with the cells that form the BBB. Al
may act by affecting the number or distribution of
cell surface charges, allowing a substance to approach
a more electroneutral membrane surface. Al selectively
inhibits saturable transport systems. Either brain to blood
(efflux) systems, such as that for Tyr-MIF-1/methionine enkephalin, blood
to brain (influx) systems, such as that for interleukin-1 alpha, can be
inhibited. The basis for the selective inhibition is unknown, but may
rely on the ability of Al to displace ions such as
calcium. Al itself is transported our of the CNS. The
ability of Al to alter the activity of the BBB is one
mechanism by which Al could affect CNS function.
Selected References
* Banks, W.A. and A.J. Kastin. Lancet ii: 1227-1229,1983.
* Banks, W.A. et al. J Pharmacol. Exp. Therap. 244: 579-585, 1988.
* Banks, W.A. and A.J. Kastin. Neurosci. Biobehav. Rev. 13:
47-53,1989.
* Vorbrodt, A.W. et al. Histochem. J. 26: 119-126, 1994.
* Banks, W.A., A.J. Kastin, and P. Zatta. In: Non-neuronal
Cells in Alzheimer's Disease. World Scientific, Singapore, pp 1-12, 1995.
* Ackley, DC and Yokel RA. Toxicology 120: 89-97, 1997.
For further information:
Prof. William A. Banks
GRECC, Veterans Affairs Medical Center St. Louis and
Saint Louis University School of Medicine,
Division of Geriatrics, Department of Internal Medicine
915 N. Grand Blvd
St. Louis, MO 63106
USA
Mail to: bankswa@slu.edu