Comparative toxicity of intracerebroventricular and subcutaneous aluminum in the rabbit

Similar patterns of neurotoxicity were produced in rabbits receiving 20 to 28 subcutaneous (sc) 400 mumol/kg injections of aluminum (Al) lactate given during 1 month and in rabbits receiving a single 2.5 to 5 mumol Al injection into each cerebral ventricle (icv). Predominant overt features of the Al-induced encephalopathy included splayed limbs, seizures and postural changes. Elevated brain Al concentrations, especially in cortical regions, were associated with behavioral changes and the development of neurofibrillary tangles (NFTs). In rabbits developing NFTs, an Al concentration of 3.5 micrograms/gm dry weight was the minimal concentration associated with tangle formation. However, no correlation was seen between brain Al concentration and the number of NFTs produced. Elevated brain Al concentrations and symptoms of Al-induced encephalopathy were seen approximately 12 days after icv and 18 days after completion of sc Al injections. The results from the present study demonstrate that the neuropathology, brain aluminum concentrations, and behavioral symptomatology produced by centrally administered Al can be replicated by administration of an adequate dose of peripherally administered Al. Furthermore, an advantage of peripheral Al administration over icv Al administration is that a longer period of time is seen between dosing and the full onset of the encephalopathy, providing more time to study the effects of Al intoxication.