POTENTIATION OF ORGANOPHOSPHORUS COMPOUND-INDUCED DELAYED NEUROTOXICITY (OPIDN) IN THE CENTRAL AND PERIPHERAL NERVOUS-SYSTEM OF THE ADULT HEN - DISTRIBUTION OF AXONAL LESIONS

Clinical manifestations of mild organophosphorus compound-induced dela yed neurotoxicity (OPIDN) produced by diisopropylphosphorofluoridate ( DFP) in adult hens are potentiated by posttreatment with phenylmethane sulfonyl fluoride (PMS). The purpose of this study was to assess wheth er potentiation of mild OPIDN produces a pattern of axonal lesions in the central and peripheral nervous system similar to that seen in seve re OPIDN. Groups of 6 hens each were given the following priming/chall enge doses sc at 0 and 4 h, respectively: 0.20 ml/kg corn oil/0.50 ml/ kg glycerol formal (GF) (control); 0.50 mg/kg DFP/GF (low-dose DFP); 0 .50 mg/kg DFP/60 mg/kg PMSF (potentiated DFP); 60 mg/kg PMSF/GF (PMSF alone); 60 mg/kg PMSF/1.5 mg/kg DFP (protected DFP); and 1.5 mg/kg DFP /GF (high-dose DFP). Two hens from each group were used to assay brain neurotoxic esterase (NTE) 24 h after the challenge dose, ana the rema ining hens were scored for deficits in walking, standing, and perching ability on d 18. Three hens from each group were perfusion-fixed on d 22 and neural tissues were prepared for histologic evaluation. DFP an d/or PMSF caused >88% brain NTE inhibition in all treated groups, comp ared to control. Protected DFP yielded no clinical deficits and a dist ribution and frequency of axonal lesions similar to control. PMSF alon e produced a small increase in the frequency of lesions in the cervica l spinal cord and peripheral nerves compared to control, Low-dose DFP caused minimal ataxia and increased frequency of axonal lesions in dor sal and lateral cervical spinal cord ventral lumbar spinal cord and in ferior cerebellar peduncles (ICP) compared to control. Potentiated DFP and high-dose DFP produced maximal ataxia and essentially identical i ncreases in the frequency of lesions in dorsal and ventral thoracic sp inal cord, lateral lumbar spinal cord, and peripheral nerves compared to low-dose DFP. The results indicate that PMSF potentiation of mild O PIDN induced in adult hens by by dose DFP results in an overall patter n of axonal degeneration like that produced by a threefold higher dose of DFP alone, and support the hypothesis that potentiation causes an increase in the frequency of axonal lesions in central and peripheral foci normally affected by OPIDN.