J. Savory et al., PARTIAL REVERSAL OF ALUMINUM-INDUCED NEUROFIBRILLARY DEGENERATION BY DESFERRIOXAMINE IN ADULT MALE RABBITS, Neuropathology and applied neurobiology, 20(1), 1994, pp. 31-37
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.