Neuroputhology zyxwvutsrqpo and Applied Neurobiology zyxwvutsr 1990, zyxwvut 16, zyxwvu 5 11-528 zyxwvuts Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits C. D. KATSETOS*t, J. SAVORY*$, M. M. HERMAN*, R. M. CARPENTER§, A. FRANKFURTERI, C. D. HEWITT* AND M. R. WILLS*II From the Departments of *Pathology, $Biochemistry, §Comparative Medicine, 7 Biology and lllnternal Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA Katsetos C.D., Savory J., Herman M.M., Carpenter R.M., Frankfurter A., Hewitt C.D. zyxwvuts & Wills M.R. (1990) Neuropathology and Applied Neurobiology 16, 51 1-528. Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits. The antigenicity of neuronal cyto- skeletal lesions was studied immunohistochemically in adult New Zealand white rabbits after intraventricular (subacute) and intravenous (chronic) administra- tion of a water-soluble aluminium compound, aluminium (Al) maltol. After short-term intraventricular administration, rabbits developed widespread neuro- fibrillary degeneration (NFD) involving pyramidal neurons of the isocortex and allocortex, projection neurons of the diencephalon, and nerve cells of the brain stem and spinal cord. There was a predilection for motor neuron involvement and for the infratentorial portions of the neuraxis. Perikarya and proximal neurites were especially affected. Bundles of 10 nm filaments were frequently present. Three of the animals treated intravenously for 12 weeks or longer displayed NFD in the oculomotor complex and in the pyramidal neurons of the occipital isocortex. Following either mode of administration, the affected neurons exhibited immunostaining with a panel of monoclonal antibodies (MAbs) against phos- phorylated (SMI-3 I), zyxwvuts non-phosphorylated/phosphatase-sensitive (SMI-32), and dephosphorylation-independent (SMI-33) epitopes of high and middle molecular weight neurofilament (NF) protein subunits. They were non-reactive with MAbs to microtubule-associated protein 2 and the class TI1 neuron- associated P-tubulin isotype. Our findings indicate that intraventricular A1 maltol produces similar, but more widespread degeneration of projection-type neurons than the less water- soluble A1 compounds as reported by others. The NFD lesions are compared with those of senile dementia of the Alzheimer type (SDAT) and motor neuron disease. Keywords: aluminium maltol, neurodegeneration, neurofilaments, phosphoryla- tion, MAP2, occipital isocortex Correspondence to: Dr Mary M. Herman, Department of Pathdlogy (Neuropathology), University of Virginia School of Medicine, Charlottesville, VA 22908, USA. ?Presently Assistant Professor at the Departments of Pathology and Laboratory Medicine, and Neurology, Hahnemann University, Philadelphia, Pennsylvania and Consultant in Neuropathology. Beth Israel Medical Center, New York, USA. 51 1