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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