Neuropathology of organophosphate-induced delayed neuropathy (OPIDN) in young chicks

Abstract

To examine the phenomenon of apparent age resistance of young chicks to organophosphate-induced delayed neuropathy (OPIDN), groups of either 2- or 10-week-old chicks were exposed subcutaneously daily for 4 days to the neuropathic organophosphate (OP), di-isopropylfluorophosphate (DFP, 1 mg/kg), the non-neuropathic OP, paraoxon (PO, 0.25 mg/kg) or atropine (20 mg/kg). Subsequently, all birds were examined at post-exposure intervals (calculated from the last day of exposure) for up to 56 days for neurological deficits and morphological lesions in the central and peripheral nervous systems (CNS, PNS). Clinically, none of the birds in the 2-week-old groups, or in the 10-week-old PO or atropine exposed groups had neurological deficits. However, all birds in the 10-week-old DFP exposed group developed ataxia by 7 days post-exposure (DPE) and then progressive paralysis. Therefore, all birds in the 10-week-old groups were killed at 14 DPE. Pathologically, the 2-week-old DFP exposed chicks had increasingly severe lesions of Wallerian-like degeneration predominantly in the spinal cord from 7 DPE and subsequently. In the 10-week-old DFP exposed chicks, the degenerative lesions of OPIDN were first detected in the CNS at 3 DPE and then with equally increasing severity in the CNS and PNS up to 14 DPE. A higher incidence of neuronal necrosis and chromatolysis in ventral motor horn neurons of spinal cord grey matter and in dorsal root ganglia occurred in both the DFP exposed age groups compared with those lesions in other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of Organophosphorus-Induced Delayed Neurotoxicity Following Phenyl Saligenin Phosphate Exposures in 2-, 5-, and 8-Week-Old Chickens

“…For example, cords from 2-week-old birds had slight amounts of degeneration but the birds were completely resistant to clinical dysfunction. These results agree with a previous study (Funk et al, 1994) following repeated DFP exposures in 2-week-old chickens. Comparison of similarly treated groups of 5-and 8-week-old birds (Figs.…”

“…Although both dorsal spinocerebellar and ventral spinocerebellar tracts have been reported in birds (Whitlock, 1952;Karten and Hodos, 1967), the present results indicate that the larger dorsal tract undergoes more severe degeneration after exposure to PSP and PSP/PMSF, a finding similar to that reported in chickens after exposure to tri-ort/10-tolyl phosphate (Tanaka and Bursian, 1989) and diisopropylphosphorofluoridate (Tanaka et al, 1990). Previous studies have hypothesized that degeneration of the dorsal spinocerebellar tract, which has been shown in chickens to terminate as mossy fiber afferents in the cerebellar cortex (Okado et al, 1987), may be closely linked to the onset of ataxia (Pope et al, 1993;Funk et al, 1994). The morphological data in the present Axonal degeneration in the dorsal columns (shaded bars) and spinocerebellar tracts (striped bars) of cervical cords from 2-, 5-, and 8-weekold chickens treated with PSP (5 mg/kg, sc) with or without PMSF (90 mg/ kg, sc).…”

“…OPIDN is usually studied in adult chickens: very young birds are completely resistant to clinical signs of OPIDN but not to the neural damage itself (Funk et al, 1994) and become more susceptible to the clinical signs as they mature (Bondy et al, 1960;Johnson and Barnes, 1970;Pope et al, 1992;Peraica etal, 1993). Experimental use of phenyl saligenin phosphate (PSP), an analog of the neuropathic metabolite of tri-ort/10-tolyl phosphate (TOTP), provides certain advantages over other commonly used neuropathic OPs.…”

Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide, diazinon

“…Second, this distinguishes developmental neurotoxicity from the loss of motor function that characterizes outright organophosphate-induced delayed neuropathy (OPIDN) as found in the adult [1]. Indeed, the developing organism is resistant to OPIDN because of the greater plasticity of developing peripheral projections [8]. There is a single previous report on the lasting behavioral effects of early DZN exposure [28] that indicates significant motor impairment in adult mice after exposure to 9 mg/kg/d throughout the entire gestational period.…”

Toxic and Metabolic Myelopathies

“…The same neuropathologic changes may be associated with prominent and diffuse spinal cord atrophy especially in the thoracic region. 42 Imaging Findings MRI at the late phase of exposure may reveal evidence of spinal cord atrophy that persists long after the cholinergic effects had subsided.…”