Aluminum and Blood-Brain Barrier Permeability

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Aluminum and Blood-Brain Barrier Permeability

Prof. A. Banks

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. 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@...

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