MULTIPLE MECHANISMS CONTRIBUTE TO MYENTERIC PLEXUS ABLATION INDUCED BY BENZALKONIUM CHLORIDE IN THE GUINEA-PIG ILEUM

Ablation of rat myenteric plexus with benzalkonium chloride has provid ed 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-F os, and on immunocytes in the guinea-pig ileum. Benzalkonium chloride (0.1%) or saline was applied to the serosal surface of distal ileum. T issues were analyzed 2, 3, or 7 days later and compared with cyclospor ine-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 an d were mostly gone after 3 days. Neuronal c-Myc began to disappear whi le 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 myen teric plexus. Populations of T cells, B cells, and macrophage-like cel ls in untreated and saline-treated myenteric plexuses were substantial ly increased 3 and 7 days after benzalkonium-chloride treatment. Cyclo sporine delayed significant neuronal loss. We conclude that a variety of degenerative mechanisms may be active in this model, including an i mmune response which may actively contribute to tissue destruction.