Correlated nerve conduction, somatosensory evoked potential and neuropathological studies in clioquinol and 2,5-hexanedione neurotoxicity in the baboon.
Observations have been made on 10 baboons receiving a high-dose regimen of clioquinol administered orally, 6 receiving a low-dose regimen and 6 treated with 2,5-hexanedione. The results were compared with those obtained from 10 control animals. Motor and sensory nerve conduction velocity was markedly reduced in the hexanedione-treated animals but only very minor abnormalities were detected in the clioquinol-treated baboons. Cervical and Rolandic somatosensory evoked potentials to lower and upper limb stimulation were delayed in both the high-dose clioquinol-treated and the hexanedione-treated animals, particularly in the latter. Histopathological studies in the low-dose clioquinol-treated group showed no abnormalities. In the high-dose group; axonal degeneration was confined to the spinal cord, cerebellar vermis and optic tract. It was most marked in the rostral portions of the dorsal spinal columns and the caudal parts of the direct and crossed corticospinal tracts. Occasional dorsal column fibres had degenerated back to the root entry zone in the cord. The distribution was that of a selective central distal axonopathy. There appeared to be no correlation with estimated blood levels of unaltered clioquinol. In hexanedione-treated animals there was also degeneration in the distal optic tracts and peripheral nerves in a pattern of central-peripheral distal axonopathy.
D000284:Administration, Oral; D000818:Animals; D001369:Axons / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects; D007464:Clioquinol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D006588:Hexanones / Q000633:toxicity*; D006912:Hydroxyquinolines / Q000633:toxicity*; D007659:Ketones / Q000633:toxicity*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects*; D009900:Optic Nerve / Q000187:drug effects; D010215:Papio; D010525:Peripheral Nerves / Q000187:drug effects; D012677:Sensation / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects
D006588:Hexanones; D006912:Hydroxyquinolines; D007659:Ketones; D007464:Clioquinol; C011269:2,5-hexanedione