MODIFICATION OF THE BLOOD-BRAIN-BARRIER THROUGH CHRONIC INTOXICATION BY ALUMINUM GLUTAMATE - POSSIBLE ROLE IN THE ETIOLOGY OF ALZHEIMERS-DISEASE

The authors have used an experimental rat model of chronic aluminum (A1) intoxication to reproduce pathological signs analogous to those observed in humans for Alzheimer's disease or dialysis encephalopathy. Preliminary chronic intoxication was achieved during 5 wk by daily subcutaneous injection of a suspension of glutamate and A1 prior to intravenous (iv) administration of sodium L-glutamate and A1 chloride. A significant increase in A1 content was observed in different areas of the brain, such as the hippocampus, the occipito-parietal cortex, the cerebellum, and the striatum. Moreover, half of the animals subcutaneously treated with A1 glutamate had neurological disturbances, such as trembling, equilibrium difficulties, and convulsions leading to death about 1 h after iv administration. A significant increase in glutamic acid at the level of the occipito-parietal cortex was found in comparison with controls, which received only sodium L-glutamate or saline solution. These results show that the A1-L-glutamate complex may well induce a modification of the blood-brain barrier.