Aluminum and Blood-Brain Barrier Permeability
by Prof. William 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.
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* 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
Mail to: firstname.lastname@example.org