Partial reversal of aluminium-induced neurofibrillary degeneration by desferrioxamine in adult male rabbits.
Desferrioxamine, a chelating agent with a high affinity for aluminium, has been reported to slow the clinical progression of dementia associated with Alzheimer's disease [4]. We report here the effects of desferrioxamine treatment on aluminium-induced neurofibrillary degeneration in rabbits. Adult male New Zealand white rabbits received a single injection of aluminium-maltolate into the lateral cerebral ventricle. Three days later, one group of rabbits was treated with intramuscular injections of desferrioxamine twice daily; a second group received saline instead of desferrioxamine. Both groups were sacrificed 4 or 5 days following initiation of desferrioxamine or saline treatment. Minimal neurofibrillary degeneration was found in two of six desferrioxamine-treated rabbits, while all six rabbits treated with saline showed extensive neurofibrillary degeneration, particularly in the ventral horn of the lower spinal cord. Quantitation of the neurofibrillary degeneration in ventral horn neurons of lumbar cord revealed 30% to be affected in saline-treated animals compared to zero-affected neurons following desferrioxamine treatment. When sacrificed just 3 days after aluminium treatment, 50% of the rabbits already revealed neurofibrillary degeneration, corresponding to the time-point when desferrioxamine treatment was begun in the above animals; on quantitation, 7.5% of ventral lumbar cord neurons were involved. These findings indicate a partial reversal of aluminium-induced neurodegeneration by desferrioxamine. Delaying desferrioxamine treatment to 6 days after aluminium administration prevented any reversal of the aluminium effect; all animals had abundant neurofibrillary degeneration as well as a striking basophilic spicular deposit of calcium and argyrophilic material in the leptomeninges, lateral ventricles and brain parenchyma adjacent to these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Savory
J
J
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908.
Herman
M M
MM
Erasmus
R T
RT
Boyd
J C
JC
Wills
M R
MR
D017607:Aluminum Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D006651:Histocytochemistry; D007276:Injections, Intraventricular; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D016874:Neurofibrillary Tangles / Q000473:pathology; D011817:Rabbits
D017607:Aluminum Compounds; D003676:Deferoxamine