Type of Document Master's Thesis Author Carboni, Deborah Ann URN etd-12052009-020159 Title Comparative evolution of mipafox-induced delayed neuropathy in the rat and hen Degree Master of Science Department Veterinary Medical Sciences Advisory Committee
Advisor Name Title Jortner, Bernard S. Committee Chair Dyer, Karen R. Committee Member Ehrich, Marion F. Committee Member Keywords
- Organophosphorus compounds
Date of Defense 1993-08-09 Availability restricted AbstractThe group of chemicals designated organophosphorus
compounds have had a significant impact on modern life, including use as pesticides, industrial plasticizers and chemical warfare agents. Exposure to certain organophosphates produces a delayed degeneration of the longest and largest
nerve fibers, including those of the ascending and descending tracts of the spinal cord, a condition termed organophosphorus ester-induced delayed neuropathy (OPIDN). Recorded incidents
of such an effect in humans have led to research regarding this neurological disease. Among the OPIDN-inducing agents is mipafox, an organophosphate insecticide, the compound we chose
to employ in our studies. Although the hen is the primary experimental model in the safety assessment of organophosphates, current research has suggested that the rat may have some validity as an experimental model. We examined the sequential neuropathic effects of a single dose of mipafox (30mg/kg) in rats and hens on a comparative basis to determine the better experimental model. Organophosphorus ester-induced
delayed neuropathy (OPIDN) has been reported in rats and hens, but sequential pathological studies exist only for the latter. We performed studies of the temporal development of bilateral
lesions elicited by 30 mg/kg of mipafox (ip) in the medulla and
cervical spinal cord of male Long-Evans rats (> 60 days of age) and White Leghorn hens (> 18 months of age). In two studies, this dosage inhibited brain neurotoxic esterase 4 hours after administration by more than 70% in both the brain and spinal cord of rats and hens. In rats, lesions were seen in distal levels of the fasciculus gracilis, and mainly consisted of numbers of swollen, vacuolated myelinated axons, restricted to
medullary levels of the tract. These varied in intensity
between animals and were seen in 5/5 on day 7, 3/3 on day 14, 4/4 on day 21, 6/8 on day 28 and 7/9 on day 35. Occasional similarly swollen fibers were seen in this region in some controls as well. Hens had extensive regions of myelinated fiber degeneration consisting of swollen, debris-laden axons progressing to allerian-like degeneration in distal (rostral) levels of spinocerebellar tracts and fasciculus gracilis.
These were seen in 1/4 on day 7, 4/4 on days 14 and 21, 3/3 on day 28 and 2/2 on day 35. The prominent central nervous system lesions of OPIDN in hens evolved in a stereotypical fashion, becoming most florid by day 21. In contrast, rats had a more erratic evolutionary course of lesion development, which did not approach the hen in severity. Resolution of these rodent neuropathic changes was seen by day 35.
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