COMPARATIVE-STUDY OF CHRONIC ALUMINUM-INDUCED NEUROFILAMENTOUS AGGREGATES WITH INTRACYTOPLASMIC INCLUSIONS OF AMYOTROPHIC-LATERAL-SCLEROSIS

Amyotrophic lateral sclerosis (ALS) is characterized neuropathological ly by chromatolysis, Bunina bodies, hyaline inclusions, skein-like inc lusions and axonal spheroids, Aluminum, a known neurotoxin, is the cau se of dialysis encephalopathy and is considered to be a causative agen t in high incidence foci of ALS in the western Pacific. We have develo ped an experimental model of motor neuron degeneration in New Zealand white rabbits using chronic low-dose intracisternal administration of aluminum and compared the clinical and neuropathological changes to th ose of human ALS. Aluminum-inoculated rabbits developed progressive hy perreflexia, hypertonia, limb splaying, gait impairment, muscle wastin g, hindlimb paralysis and impaired tonic immobility responses without overt encephalopathic features over a 14-month period. Examination of spinal cords from these animals demonstrated the frequent occurrence a nd progressive development of anterior horn cell lesions that included small, round, argentophilic perikaryal inclusions similar to hyaline inclusions seen in human ALS. Other inclusions were more condensed and eosinophilic, while still others had neurofibrillary tangle-like morp hologies. Axonal spheroids and neuritic thickenings were also prominen t and were identical to those seen in human ALS, We believe that the s imilar and progressive development of neuropathological changes observ ed in the chronic aluminum-intoxication model, compared to hu man ALS, warrants further study to aid in understanding the cellular and molec ular mechanisms of human motor neuron disease.