| Organophosphorus induced delayed neuropathy (OPIDN) is characterized by distinctive clinical and neuropathological features. The incipient clinical signs of gait disturbances and muscle weakness, are not manifest until 10-14 days post-dose. These signs of neurological impairment rapidly become exaggerated and result in paresis in severely affected animals. Axonal degeneration occurs in the long, large diameter fibers of both the central and peripheral nervous systems. Muscle spindles, in particular, have been shown to be the most sensitive neuronal targets in OPIDN.; Chickens and cats have been the species of choice in OPIDN studies because of their obvious, consistent, and reproducible clinical responses to neurotoxic organophosphorus compounds. Unlike chickens and cats, rats do not display overt clinical signs of neurological impairment. Consequently, they have been considered to be a non-susceptible species.; The biochemical initiating events which produce OPIDN involve phosphorylation and aging of a protein target site in nervous tissue. This protein has enzymatic properties and, therefore, has been termed "neurotoxic esterase" (NTE). Inhibition and aging of a threshold level of NTE inhibition ((GREATERTHEQ)70%) will predictably produce clinical signs of OPIDN in susceptible species. Therefore, it is anomalous that, although this critical level of NTE-inhibition is attained in the rat, overt clinical signs of OPIDN are not manifest.; However, neuropathological examination using a silver-gold impregnating/cholinesterase staining method revealed striking axonal degeneration in rats treated with neurotoxic organophosphorus compounds. This neuropathological pattern correlated with NTE inhibition. While there was minimal axonal degeneration and sprouting at neuromuscular junctions, muscle spindles were severely affected. In this latter structure the sensory component was the principal target. Moreover, the neuropathology in muscle spindles was consistent with all of the established distinctive hallmarks of OPIDN for chicken and cat. Therefore, while it is interesting that rats do not display obvious clinical signs, the pathological evidence indicates that rats should be considered a susceptible species. |
