Modification of the blood-brain barrier through chronic intoxication by aluminum glutamate. Possible role in the etiology of Alzheimer's disease.
The authors have used an experimental rat model of chronic aluminum (Al) 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 Al prior to intravenous (i.v.) administration of sodium L-glutamate and Al chloride. A significant increase in Al 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 Al glutamate had neurological disturbances, such as trembling, equilibrium difficulties, and convulsions leading to death about 1 h after i.v. 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 Al-L-glutamate complex may well induce a modification of the blood-brain barrier.
Deloncle
R
R
Laboratoire de Chimie Bio-Inorganique, Faculté de Pharmacie, Tours, France.
Guillard
O
O
Huguet
F
F
Clanet
F
F
D000535:Aluminum / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar
D018698:Glutamic Acid; D000535:Aluminum