title: Multiple mechanisms contribute to myenteric plexus ablation induced by benzalkonium chloride in the guinea-pig ileum.
abstract: Ablation of rat myenteric plexus with benzalkonium chloride has provided a model of intestinal aganglionosis, but the degenerative responses are not well understood. We examined the effects of this detergent on neurons and glia, including expression of c-Myc, c-Jun, JunB, and c-Fos, and on immunocytes in the guinea-pig ileum. Benzalkonium chloride (0.1%) or saline was applied to the serosal surface of distal ileum. Tissues were analyzed 2, 3, or 7 days later and compared with cyclosporine-treated and untreated animals. More than 90% of myenteric neurons were destroyed in ileal segments 3-7 days after benzalkonium-chloride treatment. Glia withdrew processes from around neurons after 2 days and were mostly gone after 3 days. Neuronal c-Myc began to disappear while c-Fos, c-Jun, and JunB were evident in some neuronal nuclei after 2 or 3 days. After 3 days, widespread apoptosis was evident in the myenteric plexus. Populations of T cells, B cells, and macrophage-like cells in untreated and saline-treated myenteric plexuses were substantially increased 3 and 7 days after benzalkonium-chloride treatment. Cyclosporine delayed significant neuronal loss. We conclude that a variety of degenerative mechanisms may be active in this model, including an immune response which may actively contribute to tissue destruction.
authors.affiliation: Neuroscience Research Group, Department of Physiology and Biophysics, The University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1.
authors.forename: E J
authors.initials: EJ
authors.lastname: Parr
authors.forename: K A
authors.initials: KA
authors.lastname: Sharkey
mesh_terms: D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016572:Cyclosporine / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000294:innervation; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D009197:Myenteric Plexus / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D011817:Rabbits; D009418:S100 Proteins / Q000032:analysis; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
chemical_list: D001548:Benzalkonium Compounds; D017252:CD3 Complex; D003902:Detergents; D007166:Immunosuppressive Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D009418:S100 Proteins; D016572:Cyclosporine; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D010751:Phosphopyruvate Hydratase