PARTIAL REVERSAL OF ALUMINUM-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 associ ated with Alzheimer's disease [4]. We report here the effects of desfe rrioxamine treatment on aluminium-induced neurofibrillary degeneration in rabbits. Adult male New Zealand white rabbits received a single in jection of aluminium-maltolate into the lateral cerebral ventricle. Th ree days later, one group of rabbits was treated with intramuscular in jections of desferrioxamine twice daily: a second group received salin e instead of desferrioxamine. Both groups were sacrificed 4 or 5 days following initiation of desferrioxamine or saline treatment. Minimal n eurofibrillary degeneration was found in two of six desferrioxamine-tr eated rabbits, while all six rabbits treated with saline showed extens ive neurofibrillary degeneration, particularly in the ventral horn of the lower spinal cord. Quantitation of the neurofibrillary degeneratio n in ventral horn neurons of lumbar cord revealed 30% to be affected i n saline-treated animals compared to zero-affected neurons following d esferrioxamine treatment. When sacrificed just 3 days after aluminium treatment, 50% of the rabbits already revealed neurofibrillary degener ation, corresponding to the timepoint when desferrioxamine treatment w as begun in the above animals; on quantitation, 7.5% of ventral lumbar cord neurons were involved. These findings indicate a partial reversa l of aluminium-induced neurodegeneration by desferrioxamine. Delaying desferrioxamine treatment to 6 days after aluminium administration pre vented any reversal of the aluminium effect; all animals had abundant neurofibrillary degeneration as well as a striking basophillic spicula r deposit of calcium and argyrophilic material in the leptomeninges, l ateral ventricles and brain parenchyma adjacent to these areas. Pre-tr eatment of rabbits with desferrioxamine did not provide the expected p rotective effect against aluminium-induced neurofibrillary degeneratio n. No pathological effects were observed when saline or desferrioxamin e were given alone, without aluminium.