Comparative evolution of mipafox-induced delayed neuropathy in rats and hens

Adult male Long-Evans rats and White Leghorn hens were given 30 mg/kg mipafox ip. Administration of this organophosphorus ester resulted in > or = 89% inhibition of brain and spinal cord neurotoxic esterase activity in both species 4 hr after dosing. Our sequential, comparative study of the bilateral mipafox-induced neuropathy in the medulla and cervical spinal cord in hens and rats demonstrated that the rats had well-developed, vacuolar axonopathic lesions in the fasciculus gracilis by post-dosing day 7. Severely affected rats with such lesions were noted through day 21, but not subsequently (days 28 and 35). The hen had a slower developing, but more severe, consistent and longer lasting neuropathy than the rat. In these birds, lesions in the medulla and rostral cervical spinal cord levels were more extensive, involving large regions of both the spinocerebellar tracts and fasciculus gracilis. Neuropathic changes, including myelinated fiber axonopathy and Wallerian-like degeneration, were prominent from days 14 - 35 in hens, and were associated with prominent gliosis in the later stages.