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Comparative dose-response studies of organophosphorus ester-induced delayed neuropathy in rats and hens administered
K R Dyer1, B S Jortner, L G Shell
1Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State Institute, Blacksburg 24061.
Abstract:
A single injection of mipafox was administered to both Long-Evans hooded rats and White Leghorn hens in dosages which inhibited the activity of brain neurotoxic esterase 30-50%, 60-80%, or greater than 80% four hr after intoxication. All animals were monitored for clinical evidence of organophosphorus induced delayed neuropathy for 21 days, euthanatized, and regions of the nervous system were histologically evaluated. Only hens manifested clinical signs of neuropathy; however, light and electron microscopic lesions were present in the nervous systems of both species. In rats, these lesions were well developed in only the highest dosage group and confined to the rostral level of the fasciculus gracilis in the medulla oblongata. Swollen axons containing a single vacuole filled with flocculent material were the most prominent lesion in rats. Hens manifested more extensive and varied fiber breakdown in multiple spinal cord tracts, with the intensity of degeneration increasing with increasing dosages of mipafox. Both marked Wallerian-like degeneration and swollen axons filled with aggregates of cellular debris were observed in the nervous systems of hens. This study indicates that both rats and hens are susceptible to OPIDN. However, there are qualitative and quantitative differences in both clinical manifestations and histologic appearances between the two species.
Insights
Both rats and hens show susceptibility to organophosphorus induced delayed neuropathy (OPIDN) after mipafox exposure. However, species-specific differences exist in clinical signs and histological damage.
Area of Science:
- Neurotoxicology
- Comparative Pathology
Background:
- Organophosphorus compounds are known neurotoxins.
- Organophosphorus induced delayed neuropathy (OPIDN) is a specific neurotoxic effect.
- Understanding species-specific responses to neurotoxins is crucial for risk assessment.
Purpose of the Study:
- To compare the susceptibility and pathological effects of mipafox, an organophosphorus compound, in rats and hens.
- To investigate the dose-dependent neurotoxic effects of mipafox on the nervous system of two different species.
Main Methods:
- Rats and hens received single injections of mipafox at varying doses.
- Animals were monitored for clinical signs of OPIDN over 21 days.
- Nervous system tissues were histologically evaluated using light and electron microscopy.
Main Results:
- Hens exhibited clinical signs of OPIDN, while rats did not, despite histological lesions in both species.
- Rats showed dose-dependent lesions primarily in the fasciculus gracilis, characterized by swollen axons with flocculent material.
- Hens displayed more widespread and severe neuropathological changes, including Wallerian-like degeneration and axonal aggregates, with severity correlating to mipafox dosage.
Conclusions:
- Both rats and hens are susceptible to mipafox-induced OPIDN.
- Significant qualitative and quantitative differences exist in clinical presentation and histological damage between rats and hens.
- These findings highlight species-specific variations in neurotoxic responses to organophosphorus compounds.
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