title: Neuronal cytoskeletal lesions induced in the CNS by intraventricular and intravenous aluminium maltol in rabbits.
abstract: The antigenicity of neuronal cytoskeletal lesions was studied immunohistochemically in adult New Zealand white rabbits after intraventricular (subacute) and intravenous (chronic) administration of a water-soluble aluminium compound, aluminium (Al) maltol. After short-term intraventricular administration, rabbits developed widespread neurofibrillary 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 phosphorylated (SMI-31), 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 III neuron-associated beta-tubulin isotype. Our findings indicate that intraventricular Al maltol produces similar, but more widespread degeneration of projection-type neurons than the less water-soluble Al compounds as reported by others. The NFD lesions are compared with those of senile dementia of the Alzheimer type (SDAT) and motor neuron disease.
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, Charlottesville 22908.
authors.forename: C D
authors.initials: CD
authors.lastname: Katsetos
authors.forename: J
authors.initials: J
authors.lastname: Savory
authors.forename: M M
authors.initials: MM
authors.lastname: Herman
authors.forename: R M
authors.initials: RM
authors.lastname: Carpenter
authors.forename: A
authors.initials: A
authors.lastname: Frankfurter
authors.forename: C D
authors.initials: CD
authors.lastname: Hewitt
authors.forename: M R
authors.initials: MR
authors.lastname: Wills
mesh_terms: D000535:Aluminum / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure*; D005260:Female; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011753:Pyrones / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D009498:Neurotoxins; D009942:Organometallic Compounds; D011753:Pyrones; C067527:aluminum maltolate; D000535:Aluminum