Aluminum alters the permeability of the blood-brain barrier to some non-peptides

Abstract

The effect of aluminum administered intraperitoneally (i.p.) on the levels of peripherally injected 99mTc labelled red blood cells in brain and on the penetration of the blood-brain barrier by radioiodinated serum albumin (RISA), thyroxine, iodide, cortisol, N-Tyr-delta sleep-inducing peptide ( N-Tyr-DSIP), growth hormone, thyroid stimulating hormone (TSH), prolactin and human and rat luteinizing hormone was examined. Treatment with aluminum did not alter the brain/blood ratio for either 99mTc red blood cells or RISA, although it did increase the blood levels of RISA. These results show that aluminum caused a contraction in the volume of plasma without altering the vascular space of the brain, disrupting the blood-brain barrier, or increasing the “leakiness” of the blood-brain barrier. Aluminum enhanced the permeability of the blood-brain barrier to labelled prolactin, thyroxine, cortisol, growth hormone, N-Tyr-DSIP and rat luteinizing hormone, but not to labelled TSH, iodide, or human luteinizing hormone, a substance with an octanol coefficient markedly different from that of luteinizing hormone from the rat. Incubation of the peptide with aluminum before injection did not increase penetration, demonstrating that aluminum did not increase the permeability of the blood-brain barrier by acting directly on the peptide. Aluminum, administered intraperitoneally, increased the accuracy of lipophilicity as a predictor of penetration of the blood-brain barrier, but the greatest increase in penetration was seen with thyroxine, a substance which crosses the blood-brain barrier by carrier-mediated transport. These results sugest that aluminum acts directly on the blood-brain barrier to enhance the permeability of membranes to lipophilic material and may also enhance carrier-mediated transport mechanisms, but that it does not disrupt the blood-brain barrier or increase its “leakiness”.