Jortner_1999_Neurotoxicol_20_971

Organophosphorus ester-induced delayed neuropathy (OPIDN) is manifest by delayed degeneration of distal levels of long myelinated fibers following an appropriate neurotoxic exposure. We investigated the dynamics of cytoskeletal changes during nerve fiber degeneration in this condition, focusing on the immunohistochemistry of axonal phosphorylated neurofilaments. OPIDN was produced in 5-month-old White Leghorn hens using a single 2.5 mg/kg intramuscular dose of phenyl saligenin phosphate. Hens were sacrificed on days 4, 7, 9, 15, and 20, and the tibial nerve branch to the gastrocnemius muscle was studied by light microscopy and immunohistochemistry (using the SMI 31 monoclonal primary antibody to phosphorylated neurofilaments). At post-dosing days 9, 15, and 20 various stages of OPIDN lesions were noted, including axonal swelling and myelinated nerve fiber degeneration. These were associated with intra-axonal cytoskeletal lysis, manifest by loss of immunolabeled phosphorylated neurofilaments, a process consistent with proteolysis. Aggregations of excess axonal phosphorylated neurofilaments were not observed.