Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound

Abstract

The effect of soman, a powerful organophosphorus (OP) cholinesterase inhibitor, was investigated in the central nervous system (CNS) of Wistar rats by neurohistology, histochemical mapping of acetylcholinesterase (AChE), and biochemical determination of cholinesterase (ChE) activity. Rats were poisoned by one lethal or sublethal subcutaneous (s.c.) injection or by several less strong weekly doses. When the acute cholinergic action of the OP led to severe respiratory failure and to repeated or prolonged convulsions, the surviving rats exhibited neuronal changes similar to those of hypoxic encephalopathy. In one case chronic intoxication gave rise to these symptoms and lesions after the fourth injection. The histochemical data showed that lesioned gray structures were generally poor in AChE. The enzymatic inhibition was quick and strong, but differed from one structure to another. ChE recovery was rapid until about 96 h after poisoning, the time course depending on the structure, but was incomplete even after 8 days. An attempt to correlate the initial level of ChE inhibition with the severity of the symptoms was not very conclusive. Our data suggest that the encephalopathy comes at least in part from complex hypoxic factors produced by the cholinergic crisis. The sequelae of slight hypoxic encephalopathy could account for some nervous long-term effects in men acutely poisoned by OP and surviving owing to mechanical ventilation.

Inhibitory Potential of Acephate and Ethanol Extract of Bacopa Monnieri on AChE in Rat Cortex and Hippocampus

“…However, the damage was prominent in frontal cortex due to soman poising. Similar histopathological alterations due to soman were reported by various investigators [32]- [34]. We can conclude that this study indicates that the ethanol extract of Bacopa moneiri may be a new potential resource of natural anticholinesterase compounds.…”

Computerized Posturography with Sway Frequency Analysis: Application in Occupational and Environmental Health.

“…On the other hand, as location of histopathological changes in the cerebellum (perivascular periodic acid-Schiff-positive exdaute, extracellular edema, focal necrosis of neurones and glias) has not been specified in previous studies on human lead poisoning [39][40][41][42] , it seems difficult to explain the functional (subclinical) changes in postural sway presented here by the histopathological findings obtained in the studies on lead poisoning. Also, neuronal degeneration and necrosis in brain including the cerebellum (vermis), similar to those in hypoxic encephalopathy, which have been observed in rats surviving convulsions after injection of soman [o-(1, 43,44) , could not explain the changes in postural sway in sarin poisoning patients, because hypoxic damage to brain was doubtful in the sarin cases as convulsion was not observed in the cases (only one case showed cardiac arrest). Histopathological changes underlying the effects of lead and sarin on postural balance remain to be investigated.…”

Animal Models That Best Reproduce the Clinical Manifestations of Human Intoxication with Organophosphorus Compounds

“…A single exposure of different animal species to high levels of soman, sarin, or VX causes profound neuropathology, with significant neuronal loss in various brain regions, including the hippocampus, amygdala, piriform cortex, and thalamus (Lemercier et al, 1983;McLeod et al, 1984;Petras, 1994;Kadar et al, 1995;Shih et al, 2003). The finding that the severity of the neuropathology induced by the nerve agents correlates well with the duration and severity of convulsions led to the suggestion that early management of nerve agentinduced convulsions would be sufficient to reduce the neuropathology and the accompanying neurologic deficits (Martin et al, 1985;Hayward et al, 1990;Lallement et al, 1993Lallement et al, , 1994Lallement et al, , 1997Lallement et al, , 1998McDonough and Shih, 1997;McDonough et al, 2000;Raveh et al, 2002;Shih et al, 2003).…”