title: Degeneration patterns in the chicken central nervous system induced by ingestion of the organophosphorus delayed neurotoxin tri-ortho-tolyl phosphate. A silver impregnation study.
abstract: Exposure to certain organophosphorus compounds results in a neurological condition known as organophosphorus-induced delayed neurotoxicity (OPIDN). OPIDN is characterized clinically by an initial post-exposure delay period of 8-14 days after which signs of progressively developing ataxia and paralysis of the hindlimbs are observed. Although several studies have reported the presence of degeneration induced by organophosphorus delayed neurotoxins in specific central nervous system (CNS) structures, none have systematically examined CNS changes seen in the most frequently studied animal model for OPIDN--the domestic fowl. In the present study, we assessed the location and extent of anterograde degeneration in the chicken CNS following exposure to tri-o-tolyl phosphate (TOTP). All birds were dosed with 500 mg TOTP/kg body weight and killed after post-exposure periods of 1, 2, 3, or 4 weeks. The brains and spinal cords were processed with Fink-Heimer and Nissl stains. In the spinal cord, axon degeneration was noted in the fasciculus gracilis at cervical levels two weeks after exposure to TOTP. At 3 weeks, degeneration was also present in the cervical part of the dorsal spinocerebellar tract, in the lumbar part of the medial pontine-spinal tract, and in lamina VII in the lumbar ventral horn. In the medulla, moderate amounts of terminal and preterminal degeneration appeared at two weeks in the lateral vestibular, gracile, external cuneate, and lateral cervical nuclei. Lesser amounts of degeneration were noted in the solitary, inferior olivary, and raphae nuclei, in the medial, descending and lateral vestibular nuclei, and in the lateral paragigantocellular, gigantocellular, and lateral reticular nuclei. Fiber degeneration was also present in the medullary portions of the dorsal and ventral spinocerebellar tracts and spinal lemniscus. In the cerebellum, moderate amounts of terminal degeneration appeared in the deep cerebellar nuclei at one week while moderate mossy fiber degeneration was first noted in the granular layers of cerebellar folia I-V at 3 weeks. These results indicate (1) that, in the CNS, axonal and terminal degeneration resulting from TOTP intoxication appears to be confined to the spinal cord, medulla and cerebellum, (2) that the time of onset of degeneration in different fiber tracts and nuclei ranges from one to three weeks post-exposure, and (3) that the delay in the appearance of clinical signs of OPIDN is consistent with the delayed onset of degeneration in many of the affected CNS fiber systems.
authors.affiliation: Department of Anatomy, Michigan State University, East Lansing 48824.
authors.forename: D
authors.initials: D
authors.lastname: Tanaka
authors.forename: S J
authors.initials: SJ
authors.lastname: Bursian
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002645:Chickens; D003408:Cresols / Q000633:toxicity*; D005260:Female; D009434:Neural Pathways / Q000473:pathology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors; D014317:Tritolyl Phosphates / Q000633:toxicity*
chemical_list: D003408:Cresols; D009943:Organophosphorus Compounds; D014317:Tritolyl Phosphates; C025541:tri-o-cresyl phosphate